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.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.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.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.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.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.tat Gene Products, Human Immunodeficiency Virus: Proteins encoded by the TAT GENES of the HUMAN IMMUNODEFICIENCY VIRUS.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.gag Gene Products, Human Immunodeficiency Virus: Proteins encoded by the GAG GENE of the HUMAN IMMUNODEFICIENCY VIRUS.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.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.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.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.env Gene Products, Human Immunodeficiency Virus: Proteins encoded by the ENV GENE of the HUMAN IMMUNODEFICIENCY VIRUS.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.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.Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.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.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.Human Immunodeficiency Virus Proteins: Proteins synthesized by HUMAN IMMUNODEFICIENCY VIRUSES such as the HIV-1 and HIV-2.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.nef Gene Products, Human Immunodeficiency Virus: Proteins encoded by the NEF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.HIV Integrase: Enzyme of the HUMAN IMMUNODEFICIENCY VIRUS that is required to integrate viral DNA into cellular DNA in the nucleus of a host cell. HIV integrase is a DNA nucleotidyltransferase encoded by the pol gene.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.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.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.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).Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.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.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.HIV Seropositivity: Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).vpr Gene Products, Human Immunodeficiency Virus: Proteins encoded by the VPR GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Reverse Transcription: The biosynthesis of DNA carried out on a template of RNA.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 Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.pol Gene Products, Human Immunodeficiency Virus: Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Virus Internalization: The entering of cells by viruses following VIRUS ATTACHMENT. This is achieved by ENDOCYTOSIS, by direct MEMBRANE FUSION of the viral membrane with the CELL MEMBRANE, or by translocation of the whole virus across the cell membrane.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.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.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).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.vif Gene Products, Human Immunodeficiency Virus: Proteins encoded by the VIF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.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.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.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.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.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.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.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.rev Gene Products, Human Immunodeficiency Virus: Proteins encoded by the REV GENES of the HUMAN IMMUNODEFICIENCY VIRUS.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).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.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.Viral Tropism: The specificity of a virus for infecting a particular type of cell or tissue.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.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)Viremia: The presence of viruses in the blood.HIV Seronegativity: Immune status consisting of non-production of HIV antibodies, as determined by various serological tests.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.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.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.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.Genes, tat: DNA sequences that form the coding region for the protein responsible for trans-activation of transcription (tat) in human immunodeficiency virus (HIV).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 The relationships of groups of organisms as reflected by their genetic makeup.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.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.HIV Long-Term Survivors: Persons who have experienced prolonged survival of HIV infection. This includes the full spectrum of untreated, HIV-infected long-term asymptomatics to those with AIDS who have survived due to successful treatment.Virus Release: Release of a virus from the host cell following VIRUS ASSEMBLY and maturation. Egress can occur by host cell lysis, EXOCYTOSIS, or budding through the plasma membrane.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.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".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.)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.Host-Pathogen Interactions: The interactions between a host and a pathogen, usually resulting in disease.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.Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.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.Pregnancy Complications, Infectious: The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION.Anti-Retroviral Agents: Agents used to treat RETROVIRIDAE INFECTIONS.Drug Resistance, Multiple, Viral: The ability of viruses to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutation.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Cytidine Deaminase: An enzyme that catalyzes the deamination of cytidine, forming uridine. EC, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.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.Genetic Variation: Genotypic differences observed among individuals in a population.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.RNA, Transfer, Lys: A transfer RNA which is specific for carrying lysine to sites on the ribosomes in preparation for protein synthesis.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Epitopes: Sites on an antigen that interact with specific antibodies.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.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.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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.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.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.Kenya: A republic in eastern Africa, south of ETHIOPIA, west of SOMALIA with TANZANIA to its south, and coastline on the Indian Ocean. Its capital is Nairobi.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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.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.Plasma: The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION.Vagina: The genital canal in the female, extending from the UTERUS to the VULVA. (Stedman, 25th 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.AIDS-Associated Nephropathy: Renal syndrome in human immunodeficiency virus-infected patients characterized by nephrotic syndrome, severe proteinuria, focal and segmental glomerulosclerosis with distinctive tubular and interstitial changes, enlarged kidneys, and peculiar tubuloreticular structures. The syndrome is distinct from heroin-associated nephropathy as well as other forms of kidney disease seen in HIV-infected patients.Senegal: A republic in western Africa, southwest of MAURITANIA and east of MALI. Its capital is Dakar.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.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.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.