Simian immunodeficiency virus: Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.Simian Acquired Immunodeficiency Syndrome: Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.Macaca mulatta: A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.SAIDS Vaccines: Vaccines or candidate vaccines designed to prevent SAIDS; (SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME); and containing inactivated SIMIAN IMMUNODEFICIENCY VIRUS or type D retroviruses or some of their component antigens.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Macaca nemestrina: A species of the genus MACACA which inhabits Malaya, Sumatra, and Borneo. It is one of the most arboreal species of Macaca. The tail is short and untwisted.HIV-2: An HIV species related to HIV-1 but carrying different antigenic components and with differing nucleic acid composition. It shares serologic reactivity and sequence homology with the simian Lentivirus SIMIAN IMMUNODEFICIENCY VIRUS and infects only T4-lymphocytes expressing the CD4 phenotypic marker.Gene Products, gag: Proteins coded by the retroviral gag gene. The products are usually synthesized as protein precursors or POLYPROTEINS, which are then cleaved by viral proteases to yield the final products. Many of the final products are associated with the nucleoprotein core of the virion. gag is short for group-specific antigen.Macaca: A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes.Gene Products, env: Retroviral proteins, often glycosylated, coded by the envelope (env) gene. They are usually synthesized as protein precursors (POLYPROTEINS) and later cleaved into the final viral envelope glycoproteins by a viral protease.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).HIV: Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Gene Products, nef: Products of the retroviral NEF GENE. They play a role as accessory proteins that influence the rate of viral infectivity and the destruction of the host immune system. nef gene products were originally found as factors that trans-suppress viral replication and function as negative regulators of transcription. nef stands for negative factor.Cercocebus atys: A species of Old World monkeys from the genera CERCOCEBUS that is important in AIDS research. They may be naturally or experimentally infected with the SIMIAN IMMUNODEFICIENCY VIRUS. They inhabit African forests from Sierra Leone to the Congo Republic.Contrecoup Injury: An injury in which the damage is located on the opposite side of the primary impact site. A blow to the back of head which results in contrecoup injury to the frontal lobes of the brain is the most common type.Genes, nef: DNA sequences that form the coding region for a protein that down-regulates the expression of human immunodeficiency virus (HIV). nef is short for negative factor.Viral Load: The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.Immunodeficiency Virus, Feline: A species of LENTIVIRUS, subgenus feline lentiviruses (LENTIVIRUSES, FELINE) isolated from cats with a chronic wasting syndrome, presumed to be immune deficiency. There are 3 strains: Petaluma (FIP-P), Oma (FIP-O) and Puma lentivirus (PLV). There is no antigenic relationship between FIV and HIV, nor does FIV grow in human T-cells.Cercopithecus: A genus of Old World monkeys found in Africa although some species have been introduced into the West Indies. This genus is composed of at least twenty species: C. AETHIOPS, C. ascanius, C. campbelli, C. cephus, C. denti, C. diana, C. dryas, C. erythrogaster, C. erythrotis, C. hamlyni, C. lhoesti, C. mitis, C. mona, C. neglectus, C. nictitans, C. petaurista, C. pogonias, C. preussi, C. salongo, and C. wolfi.Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= GENE PRODUCTS, REV), termed the rev-responsive element (RRE).RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Viremia: The presence of viruses in the blood.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.nef Gene Products, Human Immunodeficiency Virus: Proteins encoded by the NEF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Receptors, CCR5: CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.AIDS Vaccines: Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Mandrillus: A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, comprising two species: the drill (M. leucophaeus) and the mandrill (M. sphinx). They are usually found in thick rainforest and have a gentle disposition despite their ferocious reputation. Some authors consider Mandrillus a subgenus of PAPIO.Viral Regulatory and Accessory Proteins: A broad category of viral proteins that play indirect roles in the biological processes and activities of viruses. Included here are proteins that either regulate the expression of viral genes or are involved in modifying host cell functions. Many of the proteins in this category serve multiple functions.tat Gene Products, Human Immunodeficiency Virus: Proteins encoded by the TAT GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Retroviridae Proteins: Proteins from the family Retroviridae. The most frequently encountered member of this family is the Rous sarcoma virus protein.Macaca fascicularis: A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Genes, gag: DNA sequences that form the coding region for proteins associated with the viral core in retroviruses. gag is short for group-specific antigen.Cercocebus: A genus of the subfamily CERCOPITHECINAE inhabiting the African forests. They are also known as mangabeys.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Proviruses: Duplex DNA sequences in eukaryotic chromosomes, corresponding to the genome of a virus, that are transmitted from one cell generation to the next without causing lysis of the host. Proviruses are often associated with neoplastic cell transformation and are key features of retrovirus biology.Monkey Diseases: Diseases of Old World and New World monkeys. This term includes diseases of baboons but not of chimpanzees or gorillas (= APE DISEASES).Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.Feline Acquired Immunodeficiency Syndrome: Acquired defect of cellular immunity that occurs in cats infected with feline immunodeficiency virus (FIV) and in some cats infected with feline leukemia virus (FeLV).HIV Antigens: Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.Vaccinia virus: The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.gag Gene Products, Human Immunodeficiency Virus: Proteins encoded by the GAG GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Vaccines, Attenuated: Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity.Lentivirus Infections: Virus diseases caused by the Lentivirus genus. They are multi-organ diseases characterized by long incubation periods and persistent infection.HIV Reverse Transcriptase: A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.Gene Products, tat: Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.HIV Core Protein p24: A major core protein of the human immunodeficiency virus encoded by the HIV gag gene. HIV-seropositive individuals mount a significant immune response to p24 and thus detection of antibodies to p24 is one basis for determining HIV infection by ELISA and Western blot assays. The protein is also being investigated as a potential HIV immunogen in vaccines.Gene Products, vpr: Trans-acting proteins which accelerate retroviral virus replication. The vpr proteins act in trans to increase the levels of specified proteins. vpr is short for viral protein R, where R is undefined.Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.Receptors, HIV: Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120.Lentiviruses, Primate: A subgenus of LENTIVIRUS comprising viruses that produce immunodeficiencies in primates, including humans.RNA-Directed DNA Polymerase: An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.HIV Long Terminal Repeat: Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.Gene Products, pol: Retroviral proteins coded by the pol gene. They are usually synthesized as a protein precursor (POLYPROTEINS) and later cleaved into final products that include reverse transcriptase, endonuclease/integrase, and viral protease. Sometimes they are synthesized as a gag-pol fusion protein (FUSION PROTEINS, GAG-POL). pol is short for polymerase, the enzyme class of reverse transcriptase.Colobus: A genus of Old World monkeys, subfamily COLOBINAE, family CERCOPITHECIDAE, that inhabits the forests of Africa. It consists of eight species: C. angolensis (Angolan colobus), C. badius or C. rufomitratus (Red or Bay colobus), C. guereza (Guereza or Eastern black-and-white colobus), C. kirkii (Kirk's colobus), C. polykomos (King colobus or Western black-and-white colobus), C. satanas (Black colobus), and C. verus (Olive colobus). Some authors recognize Procolobus as a separate genus and then the olive colobus is recognized as the species P. verus.HIV Envelope Protein gp41: Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING.Gene Products, vif: Retrovirally encoded accessary proteins that play an essential role VIRUS REPLICATION. They are found in the cytoplasm of host cells and associate with a variety of host cell proteins. Vif stands for "virion infectivity factor".Human Immunodeficiency Virus Proteins: Proteins synthesized by HUMAN IMMUNODEFICIENCY VIRUSES such as the HIV-1 and HIV-2.vpr Gene Products, Human Immunodeficiency Virus: Proteins encoded by the VPR GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Genes, pol: DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Genes, vpr: DNA sequences that form the coding region for a trans-activator protein that specifies rapid growth in human immunodeficiency virus (HIV). vpr is short for viral protein R, where R is undefined.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for retroviral replication. Specifically, the rev gene products are required for processing and translation of the gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion.Receptors, CXCR4: CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.HIV Seropositivity: Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).Vaccines, Synthetic: Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.Vagina: The genital canal in the female, extending from the UTERUS to the VULVA. (Stedman, 25th ed)Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Organophosphonates: Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Pan troglodytes: The common chimpanzee, a species of the genus Pan, family HOMINIDAE. It lives in Africa, primarily in the tropical rainforests. There are a number of recognized subspecies.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.vif Gene Products, Human Immunodeficiency Virus: Proteins encoded by the VIF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Genetic Variation: Genotypic differences observed among individuals in a population.rev Gene Products, Human Immunodeficiency Virus: Proteins encoded by the REV GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.Genes, rev: DNA sequences that form the coding region for a protein that regulates the expression of the viral structural and regulatory proteins in human immunodeficiency virus (HIV). rev is short for regulator of virion.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.HIV Envelope Protein gp160: An envelope protein of the human immunodeficiency virus that is encoded by the HIV env gene. It has a molecular weight of 160,000 kDa and contains numerous glycosylation sites. It serves as a precursor for both the HIV ENVELOPE PROTEIN GP120 and the HIV ENVELOPE PROTEIN GP41.Genes, Viral: The functional hereditary units of VIRUSES.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Retroviruses, Simian: Classes of retroviruses for which monkeys or apes are hosts. Those isolated from the West African green monkey and the Asian rhesus macaque monkey are of particular interest because of their similarities to viruses causing cancer and acquired immunodeficiency syndrome (AIDS) in humans.Vaccines, DNA: Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.Genes, vpu: DNA sequences that form the coding region for the HIV-1 regulatory protein vpu (viral protein U) that greatly increases the export of virus particles from infected cells. The vpu genes are not present in HIV-2 or SIMIAN IMMUNODEFICIENCY VIRUS.Genes, tat: DNA sequences that form the coding region for the protein responsible for trans-activation of transcription (tat) in human immunodeficiency virus (HIV).Virus Integration: Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA; (LYSOGENY); to form a PROPHAGE or integration of retroviral DNA into cellular DNA to form a PROVIRUS.Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.Primate Diseases: Diseases of animals within the order PRIMATES. This term includes diseases of Haplorhini and Strepsirhini.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Fusion Proteins, gag-pol: Polyprotein products of a fused portion of retroviral mRNA containing the gag and pol genes. The polyprotein is synthesized only five percent of the time since pol is out of frame with gag, and is generated by ribosomal frameshifting.Retroviridae Infections: Virus diseases caused by the RETROVIRIDAE.RNA Viruses: Viruses whose genetic material is RNA.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.HIV Protease: Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.Virus Cultivation: Process of growing viruses in live animals, plants, or cultured cells.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.CD4-CD8 Ratio: Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Haplorhini: A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes).Mucous Membrane: An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Epitopes: Sites on an antigen that interact with specific antibodies.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.AIDS Dementia Complex: A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40)Chimera: An individual that contains cell populations derived from different zygotes.Genes, vif: DNA sequences that form the coding region for the vif (virion infectivity factor) protein that is important for the generation of infectious virions in human immunodeficiency virus (HIV). The former name of this gene was sor (short open reading frame).Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Immunization, Secondary: Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Deoxyepinephrine: Sympathomimetic, vasoconstrictor agent.Viral Proteins: Proteins found in any species of virus.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Cytopathogenic Effect, Viral: Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses.Immunity, Mucosal: Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.Reassortant Viruses: Viruses containing two or more pieces of nucleic acid (segmented genome) from different parents. Such viruses are produced in cells coinfected with different strains of a given virus.Severe Combined Immunodeficiency: Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human Severe Combined Immunodeficiency (SCID).Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Retroviridae Proteins, Oncogenic: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.Superinfection: A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies.Immunodeficiency Virus, Bovine: The type species of LENTIVIRUS, subgenus bovine lentiviruses (LENTIVIRUSES, BOVINE), found in cattle and causing lymphadenopathy, LYMPHOCYTOSIS, central nervous system lesions, progressive weakness, and emaciation. It has immunological cross-reactivity with other lentiviruses including HIV.PrimatesHIV Seronegativity: Immune status consisting of non-production of HIV antibodies, as determined by various serological tests.Virus Shedding: The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (INFECTIOUS DISEASE TRANSMISSION, VERTICAL).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Cyclophilin A: A 17-KDa cytoplasmic PEPTIDYLPROLYL ISOMERASE involved in immunoregulation. It is a member of the cyclophilin family of proteins that binds to CYCLOSPORINE.Infectious Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding.Cercopithecidae: The family of Old World monkeys and baboons consisting of two subfamilies: CERCOPITHECINAE and COLOBINAE. They are found in Africa and part of Asia.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Rectum: The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Lentivirus: A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Virus Latency: The ability of a pathogenic virus to lie dormant within a cell (latent infection). In eukaryotes, subsequent activation and viral replication is thought to be caused by extracellular stimulation of cellular transcription factors. Latency in bacteriophage is maintained by the expression of virally encoded repressors.Viral Fusion Proteins: Proteins, usually glycoproteins, found in the viral envelopes of a variety of viruses. They promote cell membrane fusion and thereby may function in the uptake of the virus by cells.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Defective Viruses: Viruses which lack a complete genome so that they cannot completely replicate or cannot form a protein coat. Some are host-dependent defectives, meaning they can replicate only in cell systems which provide the particular genetic function which they lack. Others, called SATELLITE VIRUSES, are able to replicate only when their genetic defect is complemented by a helper virus.Disease Transmission, Infectious: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal or vertical (INFECTIOUS DISEASE TRANSMISSION, VERTICAL).Retroviridae: Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Cercopithecinae: A subfamily of the Old World monkeys, CERCOPITHECIDAE. They inhabit the forests and savannas of Africa. This subfamily contains the following genera: CERCOCEBUS; CERCOPITHECUS; ERYTHROCEBUS; MACACA; PAPIO; and THEROPITHECUS.Erythrocebus patas: A species of the genus ERYTHROCEBUS, subfamily CERCOPITHECINAE, family CERCOPITHECIDAE. It inhabits the flat open arid country of Africa. It is also known as the patas monkey or the red monkey.Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cameroon: A republic in central Africa lying east of CHAD and the CENTRAL AFRICAN REPUBLIC and west of NIGERIA. The capital is Yaounde.Virus Diseases: A general term for diseases produced by viruses.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Administration, Intravaginal: The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Cytidine Deaminase: An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.

RANTES, IFN-gamma, CCR1, and CCR5 mRNA expression in peripheral blood, lymph node, and bronchoalveolar lavage mononuclear cells during primary simian immunodeficiency virus infection of macaques. (1/2811)

Primary infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) (as a model of HIV infection in humans) represents a unique opportunity to study early lentivirus/host interactions. We sought to determine whether there is a temporal relationship linking SIV replication and dissemination and the expression of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) and the SIV/HIV coreceptor CCR5 in different tissues during acute SIV infection of macaques. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate of SIVmac251. RT-PCR was used to monitor the expression of RANTES and CCR5 mRNA in fresh isolated mononuclear cells from blood, lymph node, and bronchoalveolar lavages. These expressions were compared to those of IFN-gamma as an indicator of the development of the immune response and to another receptor for RANTES, CCR1, which is not described as a coreceptor for SIV/HIV-1 entry. An enhancement of CCR1/CCR5 mRNA expression was noticed during primary SIVmac251 infection of macaques, mainly in tissue. In the three different compartments investigated, IFN-gamma and RANTES overexpression was noticed by the time of systemic viral replication containment. Our results put CCR5 and RANTES mRNA expression back in the context of inflammatory and immune responses to SIV primary infection.  (+info)

Effect of the attenuating deletion and of sequence alterations evolving in vivo on simian immunodeficiency virus C8-Nef function. (2/2811)

The simian immunodeficiency virus macC8 (SIVmacC8) variant has been used in a European Community Concerted Action project to study the efficacy and safety of live attenuated SIV vaccines in a large number of macaques. The attenuating deletion in the SIVmacC8 nef-long terminal repeat region encompasses only 12 bp and is "repaired" in a subset of infected animals. It is unknown whether C8-Nef retains some activity. Since it seems important to use only well-characterized deletion mutants in live attenuated vaccine studies, we analyzed the relevance of the deletion, and the duplications and point mutations selected in infected macaques for Nef function in vitro. The deletion, affecting amino acids 143 to 146 (DMYL), resulted in a dramatic decrease in Nef stability and function. The initial 12-bp duplication resulted in efficient Nef expression and an intermediate phenotype in infectivity assays, but it did not significantly restore the ability of Nef to stimulate viral replication and to downmodulate CD4 and class I major histocompatibility complex cell surface expression. The additional substitutions however, which subsequently evolved in vivo, gradually restored these Nef functions. It was noteworthy that coinfection experiments in the T-lymphoid 221 cell line revealed that even SIVmac nef variants carrying the original 12-bp deletion readily outgrew an otherwise isogenic virus containing a 182-bp deletion in the nef gene. Thus, although C8-Nef is unstable and severely impaired in in vitro assays, it maintains some residual activity to stimulate viral replication.  (+info)

Lentivirus vectors using human and simian immunodeficiency virus elements. (3/2811)

Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34(+) cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.  (+info)

Early short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine treatment favorably alters the subsequent disease course in simian immunodeficiency virus-infected newborn Rhesus macaques. (4/2811)

Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful animal model of human pediatric AIDS to study disease pathogenesis and to develop intervention strategies aimed at delaying disease. In the present study, we demonstrate that very early events of infection greatly determine the ultimate disease course, as short-term antiviral drug administration during the initial viremia stage significantly delayed the onset of AIDS. Fourteen newborn macaques were inoculated orally with uncloned, highly virulent SIVmac251. The four untreated control animals showed persistently high virus levels and poor antiviral immune responses; they developed fatal immunodeficiency within 15 weeks. In contrast, SIV-infected newborn macaques which were started on 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) treatment at 5 days of age and continued for either 14 or 60 days showed reduced virus levels and enhanced antiviral immune responses. This short-term PMPA treatment did not induce detectable emergence of SIV mutants with reduced in vitro susceptibility to PMPA. Although viremia increased in most animals after PMPA treatment was withdrawn, all animals remained disease-free for at least 6 months. Our data suggest that short-term treatment with a potent antiviral drug regimen during the initial viremia will significantly prolong AIDS-free survival for HIV-infected infants and adults.  (+info)

Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines. (5/2811)

We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effective against the uncloned virus, SIVmne. In the present study, we examine the protective efficacy of this immunization regimen against infection by a mucosal route. We found that the same gp160-based vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne. Protection against mucosal infection is therefore achievable by parenteral immunization with recombinant envelope vaccines. Protection appears to correlate with high levels of SIV-specific antibodies and, in animals protected against the uncloned virus, the presence of serum-neutralizing activities. To understand the basis for the differential efficacies against the uncloned virus by the intravenous versus the intrarectal routes, we examined viral sequences recovered from the peripheral blood mononuclear cells of animals early after infection by both routes. We previously showed that the majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences homologous to the molecular clone from which the vaccines were made (E11S type), with the remainder (15%) containing multiple conserved changes (the variant types). In contrast to intravenously infected animals, from which either E11S-type or the variant type V1 sequences could be recovered in significant proportions, animals infected intrarectally had predominantly E11S-type sequences. Preferential transmission or amplification of the E11S-type viruses may therefore account in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route.  (+info)

Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. (6/2811)

To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.  (+info)

Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses. (7/2811)

To determine the role of viral burden in simian-human immunodeficiency virus (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were measured after inoculation of rhesus monkeys with four different SHIVs. These SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu derived from either cell line-passaged or primary patient isolates of human immunodeficiency virus type 1; the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P and SHIV-KB9 cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highest during primary infection in monkeys infected with SHIV-89.6P, the virus that caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infections that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KB9. SHIV-89. 6P uniformly caused rapid and profound CD4(+) T cell depletion and immunodeficiency. Infection with the SHIV-KB9 resulted in very low CD4(+) T cell counts without seroconversion in some monkeys and a substantial but less profound CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important role in AIDS virus pathogenesis.  (+info)

Secretion of beta-chemokines by bronchoalveolar lavage cells during primary infection of macaques inoculated with attenuated nef-deleted or pathogenic simian immunodeficiency virus strain mac251. (8/2811)

Primary infection of macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus (HIV) infection represents a unique opportunity to investigate early lentivirus-host interactions. In order to gain insight into immunopathogenic events taking place in the lung during lentiviral infection, we analysed lymphocyte expansion in the lung and chemokine secretion by mononuclear cells obtained by bronchoalveolar lavage (BALMCs) during primary infection by a pathogenic and a non-pathogenic SIV. Two groups of cynomolgus macaques were inoculated intravenously with a fully pathogenic isolate of SIVmac251 or with an attenuated, nef-deleted, molecular clone of SIVmac251. Spontaneous MIP-1alpha, MIP-1beta and RANTES production was assessed by ELISA in supernatants of short-term cultured BALMCs. Kinetics of haematological, virological and immunological parameters were investigated simultaneously. All 11 inoculated animals became infected. Monkeys inoculated with the nef-deleted SIV clone exhibited a significantly reduced plasma virus load and a less pronounced accumulation of lymphocytes in the lung compared to monkeys infected with the pathogenic SIVmac251 isolate. Compared to pre-infection levels, we observed an increase in the levels of RANTES, MIP1-alpha and MIP1-beta production in the two groups of monkeys, by the time of peak viraemia. Strikingly, a greater enhancement of RANTES and MIP-1alpha production was detected in monkeys infected with the attenuated virus. Given the potential influence of beta-chemokines on the immune response and virus replication, such results suggest that RANTES, MIP1-alpha and MIP1-beta could contribute to the singular features of the immune response elicited during infection of macaques with an attenuated SIV.  (+info)

  • The early events during infection with an immunodeficiency virus were followed by application of pathogenic simian immunodeficiency virus atraumatically to the tonsils of macaques. (sciencemag.org)
  • Virologic and immunologic events during the initial period of human immunodeficiency virus-type 1 (HIV-1) infection have important consequences for vaccine design and the eventual clinical course ( 1 , 2 ). (sciencemag.org)
  • The level of virus or set-point that develops after acute infection correlates with the rapidity with which the disease develops and acquired immunodeficiency syndrome (AIDS) appears ( 3 ). (sciencemag.org)
  • These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4(+) T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function. (pasteur.fr)
  • Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. (umassmed.edu)
  • Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naive control animals. (umassmed.edu)
  • Here we used the rhesus macaque-simian immunodeficiency virus (SIV) animal model of HIV infection to study the range of viral genotypes that are transmitted by different routes of inoculation and by different types of viral inocula. (northwestern.edu)
  • A post we made last week suggested a new vaccine can protect macaques against the monkey equivalent of HIV , however the vaccine using the common virus cytomegalovirus (CMV) as the vector or container of proteins from the simian immunodeficiency virus (SIV) protected none of a group of 24 rhesus macaques from infection. (lass.org.uk)
  • The vaccine tested enclosed SIV components within the shell of another virus which establishes an ongoing but non-pathogenic infection. (lass.org.uk)
  • After this, however, SIV virus suddenly appeared in the blood and soon established itself at normal levels, and the subsequent course of infection was similar to that in the other controls. (lass.org.uk)
  • However in just over half (13) of the CMV-vaccinated animals, the subsequent infection resembled those seen in 'elite controllers': after an initial spike of virus in the blood, they quickly achieved an almost-complete control over their virus, maintaining viral loads under 30 copies/ml with occasional 'blips', usually to no more than 1000 copies/ml. (lass.org.uk)
  • In this study, we used single-genome amplification, amplicon sequencing ( gene), and phylogenetic analyses to compare the genetic structures of simian immunodeficiency virus (SIV) populations across all the male genital organs and blood in intravenously inoculated cynomolgus macaques in the chronic stage of infection. (archives-ouvertes.fr)
  • To facilitate the identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral simian-human immunodeficiency virus (SHIV) SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. (asm.org)
  • We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or after ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. (asm.org)
  • Furthermore, we monitored SHIV replication and rebound kinetics in infant and adult RMs and found that both infants and adults demonstrated equally potent virus-specific humoral immune responses. (asm.org)
  • Researchers have hypothesized that SIVs led to the transmission of HIV (human immunodeficiency virus) in humans. (historyofvaccines.org)
  • The group found that a viral protein known to help the virus evade the immune system, thereby allowing the SIVs that infect monkeys to persist and multiply with high efficiency, also has a protective role in the host immune system. (keephopealive.org)
  • What these viruses have in common is a Vpu gene, not found in other SIVs, and so it's tempting to speculate that the presence of Vpu is somehow causally related to the change in Nef function," Dr. Sharp added. (keephopealive.org)
  • We found that a more diverse population of SIV genetic variants was present in the earliest virus-positive plasma samples from all five IV SIVmac251-inoculated monkeys and from two of five IVAG SIVmac251-inoculated monkeys. (northwestern.edu)
  • This demonstrates that receptor binding to the outer envelope glycoprotein induces certain conformational changes which are common to all of these viruses and others which are restricted to cell line-passaged isolates of HIV-1. (ox.ac.uk)
  • We report the construction and characterization of several replication- competent simian immunodeficiency virus (SIV) vectors with a deletion in the viral nef gene (SIV(Δnef)) that express gamma interferon (IFN-γ). (uthscsa.edu)
  • Giavedoni, LD & Yilma, T 1996, ' Construction and characterization of replication-competent simian immunodeficiency virus vectors that express gamma interferon ', Journal of Virology , vol. 70, no. 4, pp. 2247-2251. (uthscsa.edu)
  • Intriguingly, this loss of Nef-mediated suppression of T cell activation appears to have occurred twice, once in the ancestor of a group of viruses infecting Cercopithecus monkeys, and once in SIVcpz, the ancestor of HIV-1 which infects chimpanzees," noted study coauthor Dr. Paul Sharp, of the University of Nottingham, who is a leading expert in HIV and SIV evolution. (keephopealive.org)
  • The authors also found that SAMHD1 expression could be reduced by ex vivo treatment with the simian immunodeficiency virus protein Vpx, which was previously shown to target SAMHD1 for proteasomal degradation. (sciencemag.org)
  • Plasmids containing full-length proviral genomes were used to obtain high-titer stocks of each recombinant virus in cell cultures. (uthscsa.edu)
  • Our data suggest that the envelope from the neurovirulent SIV/17E-Fr interacts with CCR5 in a CD4-independent manner, and changes in the TM protein of this virus are important components that contribute to neurovirulence in SIV. (elsevier.com)
  • Envelope-modified single-cycle simian immunodeficiency virus selective" by Michael D. Alpert, Andrew R. Rahmberg et al. (umassmed.edu)
  • The expression of the cytokine gene was controlled either by the simian virus 40 early promoter or by the SIV 5' long terminal repeat regulatory sequences, utilizing the nef gene splice signals. (uthscsa.edu)
  • The findings suggest that the gene function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans. (keephopealive.org)
  • While altering HIV's Nef gene may not be a therapeutic possibility for those infected with the virus, these results - along with research conducted by several other teams - suggest the use of treatments that could carefully limit immune system activation in humans. (keephopealive.org)
  • For transduction, a retroviral vector system, particle-mediated transfer (gene gun), and a lentiviral vector based on simian immunodeficiency virus were investigated. (biomedcentral.com)
  • Cells (500,000) were injected directly into the knee joinst of mice with severe combined immunodeficiency (SCID). (biomedcentral.com)
  • Immune responses in CD8 T-cells to the SIV gag and pol viruses remained strong throughout the follow-up period on CMV-vaccinated animals. (lass.org.uk)
  • Early viral replication and profound CD4 + T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). (pubmedcentralcanada.ca)
  • To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four-amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). (ox.ac.uk)
  • Direct measurement of CD8+ T cell responses in macaques infected with simian immunodeficiency virus. (ox.ac.uk)
  • Myeloid dendritic cells (mDC) are lost from blood in individuals with human immunodeficiency virus (HIV) infection but the mechanism for this loss and its relationship to disease progression are not known. (prolekare.cz)
  • The overall impact of T reg cells on HIV/simian immunodeficiency virus (SIV) disease progression remains controversial and has proven difficult to assess due to lack of specific inhibitors of T reg -cell activity and the complex role of immune activation in HIV/SIV disease. (lww.com)
  • Xenotropic murine leukemia virus-related virus ( XMRV ) is a retrovirus which was first described in 2006 as an apparently novel human pathogen found in tissue samples from men with prostate cancer . (wikipedia.org)
  • We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). (pubmedcentralcanada.ca)
  • To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. (asm.org)
  • We studied the release of tumor necrosis factor-α (TNFα), a vital immunoregulatory cytokine, by alveolar macrophages (M∅s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. (elsevier.com)
  • There was no correlation between virus load and M. avium load in coinfected lymph nodes, and, with one exception, there was no evidence that M. avium coinfection of macrophages increased SIV replication. (umn.edu)
  • virus-infected macrophages appear orange/yellow (arrows). (eurekalert.org)
  • Chronic bee paralysis virus, Chimpanzee stool associated circular ssDNA virus, Circovirus-like genome RW-C, Circovirus-like genome CB-A, Rodent stool-associated circular genome virus, etc. (nih.gov)
  • Some of these may already have been present within the initial virus, and others may be coded for by the viral genome for production within the host cell. (thefreedictionary.com)
  • The 400 known viruses are classified in several ways: by genome core (RNA or DNA), host (animals, plants, or bacteria), method of reproduction (such as retrovirus), mode of transmission (such as enterovirus), and disease produced (such as hepatitis virus). (thefreedictionary.com)
  • A retrovirus is a type of RNA virus that inserts a copy of its genome into the DNA of a host cell that it invades, thus changing the genome of that cell. (wikipedia.org)
  • Once inside the host cell's cytoplasm , the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). (wikipedia.org)
  • MLVs belong to the virus family Retroviridae and the genus gammaretrovirus and have a single-stranded RNA genome that replicates through a DNA intermediate. (wikipedia.org)
  • In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. (nature.com)
  • NCps, closely associated with the dimeric RNA genome in the core of the virus particle, were shown to promote the specific encapsidation of the viral RNA and are implicated in reverse transcription. (archives-ouvertes.fr)
  • In addition, other chemokine receptors such as CCR2b and CCR3 can function as coreceptors for some viruses, and some viruses can use more than one chemokine receptor ( 3 , 5 , 8 ). (pnas.org)
  • Acquisition of the ability to use additional chemokine receptors may broaden viral host range and enable the virus to evade selective pressures against CCR5 usage, such as high levels of the CCR5 ligands RANTES, MIP-1α, and MIP-1β, which have anti-viral properties ( 20 , 21 ). (pnas.org)
  • For 10 months after inoculation, biweekly to monthly serum samples obtained from the monkey were negative for SIV antibody by whole-virus EIA and by synthetic peptide ElAs, and the monkey showed no evidence of SIV infection by PCR. (wisc.edu)
  • To explore differential regulation of Gag and Env antibody responses, immunocompetent BALB/c and T cell deficient nude mice were immunized with virus like particles (VLP) of simian immunodeficiency virus or adenoviral vectors expressing SIV Gag and Env. (biomedcentral.com)
  • These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4(+) T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function. (pasteur.fr)
  • Furthermore, the discovery of endogenous viral elements (EVEs) in the genomes of mammals, birds and other eukaryotes shows that viruses similar to contemporary virus species existed tens of millions of years ago. (nature.com)
  • Current antiretroviral therapy (ART), while effective at reducing viral loads, does not eliminate the virus, thus requiring HIV-infected individuals to remain on ART for life. (frontiersin.org)
  • To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. (asm.org)
  • HIV research efforts have long focused on prevention and developing antiretroviral therapies that keep the virus in check without eradicating it, essentially transforming HIV into a manageable chronic condition, says Lucio Gama, Ph.D. , assistant professor of molecular and comparative pathobiology at Johns Hopkins and the lead author of the new study. (eurekalert.org)
  • We have shown that chronic binge alcohol (CBA) administration (13-14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. (mdpi.com)
  • This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. (pubmedcentralcanada.ca)
  • Initial reports erroneously linked the virus to prostate cancer and later to chronic fatigue syndrome (CFS), leading to considerable interest in the scientific and patient communities, investigation of XMRV as a potential cause of multiple medical conditions, and public-health concerns about the safety of the donated blood supply . (wikipedia.org)
  • Our results suggest that viral tropism may be influenced not only by the coreceptors used by a given virus strain but also by how a given coreceptor is used. (pnas.org)
  • The chemokine receptor repertoire used by a given virus strain plays an important role in governing viral tropism. (pnas.org)