TY - JOUR. T1 - Multicenter evaluation of quantification methods for plasma human immunodeficiency virus type 1 rna. AU - Lin, Hsiang Ju. AU - Myers, Lawrence E.. AU - Yen-Lieberman, Belinda. AU - Blaine Hollinger, F.. AU - Henrard, Denis. AU - Hooper, Carol J.. AU - Kokka, Robert. AU - Kwok, Shirley. AU - Rasheed, Suraiya. AU - Vahey, Maryanne. AU - Winters, Mark A.. AU - Mc Quay, Lisa J.. AU - Nara, Peter L.. AU - Reichelderfer, Patricia. AU - Coombs, Robert W.. AU - Brooks Jackson, J.. PY - 1994. Y1 - 1994. N2 - Six procedures for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated by nine laboratories. The procedures differed in their sample volume and preparation of samples and methods of amplification and detection. Coded samples in a IO-folddilution series of HIV-L-spiked plasma were correctly ranked by all six procedures. Subsequently, coded duplicate plasma samples from 16 HIV-I-infected patients were tested using a common set of standards. Several HIV-1 ...
This is an open-label (all people know the identity of the intervention), multi-center (study conducted at multiple sites), uncontrolled (all the patients receiving darunavir) clinical and observational study (study in which the investigators/physicians observe the patients and measure their outcomes) to evaluate the safety and effectiveness of darunavir for the treatment human immunodeficiency virus-type 1 (HIV-1) infection among adult Filipino patients. The study will enroll 10 percentage of patient who would use the product, as a requirement of the Philippine Food and Drug Administration (FDA). Patients will be monitored from baseline and every 4 weeks thereafter for a period of 24 weeks. Safety evaluations for adverse events, clinical laboratory tests, physical examination, concomitant medications, and co-morbid conditions will be monitored throughout the study. The duration of treatment will be for 24 weeks and the total study will be conducted for 3 years ...
This is an open-label (all people know the identity of the intervention), multi-center (study conducted at multiple sites), uncontrolled (all the patients receiving darunavir) clinical and observational study (study in which the investigators/physicians observe the patients and measure their outcomes) to evaluate the safety and effectiveness of darunavir for the treatment human immunodeficiency virus-type 1 (HIV-1) infection among adult Filipino patients. The study will enroll 10 percentage of patient who would use the product, as a requirement of the Philippine Food and Drug Administration (FDA). Patients will be monitored from baseline and every 4 weeks thereafter for a period of 24 weeks. Safety evaluations for adverse events, clinical laboratory tests, physical examination, concomitant medications, and co-morbid conditions will be monitored throughout the study. The duration of treatment will be for 24 weeks and the total study will be conducted for 3 years ...
Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells efficiently. Monocytes that were irradiated to assure no DNA synthesis could also be readily infected with HIV-1BaL. Such infections were associated with the integration of HIV-1BaL DNA into the high molecular weight, chromosomal DNA of monocytes. Thus, normal, nonproliferating monocytes differ from T lymphocytes in that a productive HIV-1 infection can occur independently of cellular DNA synthesis. These results suggest that normal nonproliferating mononuclear phagocytes, which are relatively resistant to the destructive effects of this virus, may serve as persistent and productive reservoirs for HIV-1 in vivo. ...
Vpr and vpu are important for efficient human immunodeficiency virus type 1 replication and CD4(+) T-cell depletion in human lymphoid tissue ex ...
We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls, n = 14) in Malawi.
Five hepatoma cell lines, including CZHC/8571, PLC/PRF/5, Hep3B, HepG2, and HUH7, were inoculated with three diverse isolates of human immunodeficiency virus type 1 (HIV-1). Productive infection was noted in all hepatoma cell lines, and expression of viral p24 antigen lasted for over 3 months, but its level decreased in proportion to the number of viable cells. HIV-1 antigens were also found in the cells by immunohistochemical staining and radioimmunoprecipitation assay, as were viral RNA by in situ hybridization and HIV-1-like particles by electron microscopy. Virus yield assays were also positive on supernatant fluids collected from hepatoma cultures inoculated with HIV-1. Despite their susceptibility to infection, all five hepatoma cell lines were negative for CD4 by immunofluorescence and for CD4 mRNA by slot-blot hybridization. In addition, HIV-1 infection of hepatoma cell lines was not blocked by anti-CD4 monoclonal antibody or soluble CD4. Together, these findings clearly demonstrate that ...
Human immunodeficiency virus type 1 (HIV-1) accessory genes including nef, vif, and vpr are important factors that determine the replication and pathogenesis of HIV-1. The state of activation is also important for the replication of HIV-1. We evaluated the properties of nef-, vif-, and vpr-minus macrophage-tropic HIV-1(JR) CSF in primary CD4+ Th1- or Th2-like cell cultures which had been activated through CD3 molecules in the presence of interleukin-2 (IL-2) and IL-12 (Th1-like culture) or IL-4 (Th2-like culture), respectively. In activated Th1- or Th2-like cultures, replication of nef-minus HIV-1(JR-CSF) was markedly lower than that of wild-type HIV-1. Subsequent analysis by site-directed mutagenesis showed that (i) the presence of an acidic amino acid-rich domain (amino acid residues 72 to 75) in the Nef protein was critical for the enhancement of viral DNA synthesis, resulting in increased virus growth rate, and (ii) prolines that form part of Src homology 3 binding domain were not essential ...
TY - JOUR. T1 - Chimeric toxins targeted to the human immunodeficiency virus type 1 envelope glycoprotein augment the in vivo activity of combination antiretroviral therapy in thy/liv-SCID-Hu mice. AU - Goldstein, Harris. AU - Pettoello-Mantovani, Massimo. AU - Bera, Tapan K.. AU - Pastan, Ira H.. AU - Berger, Edward A.. PY - 2000. Y1 - 2000. N2 - Highly active antiretroviral therapy (HAART), which combines multiple inhibitors of essential human immunodeficiency virus type 1 (HiV-1) enzymes, induces dramatic and sustained viral load reductions in many people infected with HIV-1. However, reservoirs of infected cells capable of producing replication-competent virus persist even after years of HAART, preventing elimination of infection. CD4-PE40 and 3B3(Fv)-PE38, chimeric toxins designed to target the HIV envelope (Env), represent a complementary class of agents that selectively kill productively infected cells. To investigate whether these Env-targeted toxins might serve as adjuncts to HAART for ...
TY - JOUR. T1 - Longitudinal studies of viral sequence, viral phenotype, immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses. AU - Hutto, Cecelia. AU - Zhou, Y. I.. AU - Jun, H. E.. AU - Geffin, Rebeca. AU - Hill, Martin. AU - Scott, Walter. AU - Wood, Charles. PY - 1996/12/1. Y1 - 1996/12/1. N2 - Perinatal human immunodeficiency virus type 1 (HIV-1) infections cause a broad spectrum of clinical disease and are variable in both the age of the patient at onset of serious disease and the progression of the clinical course. Heterozygotic perinatally infected twins with a marked difference in their clinical courses were monitored during the first 2 years of life. Twin B, the second-born twin, developed AIDS by 6 months of age and died at 22 months of age, while twin A remained minimally symptomatic through the first 2 years. Sequential blood specimens were obtained from the twins in order to characterize the ...
The occurrence of clinical manifestations associated with primary human immunodeficiency virus type 1 (HIV-1) infection was evaluated in a prospective cohort study of female sex workers in Mombasa, Kenya. Among 103 women who seroconverted to HIV-1, fever, vomiting, diarrhea, headache, arthralgia, myalgia, skin rash, swollen lymph nodes, extrainguinal lymphadenopathy, inguinal lymphadenopathy, and vaginal candidiasis were noted significantly more frequently at visits in which seroconversion first became evident. Eighty-one percent of seroconverting women had ≥1 of these 11 symptoms or signs. Among 44% of the women, the acute illness was severe enough to prevent them from working. Having ≥2 of 6 selected symptoms and signs yielded a sensitivity of 51%, specificity of 83%, positive likelihood ratio of 3.2, and negative likelihood ratio of 0.5 for acute HIV-1 infection. The recognition of primary HIV-1-infection illness in high-risk populations and subsequent risk-reduction counseling could ...
TY - JOUR. T1 - Maternofetal Transmission of AIDS. T2 - Frequency of Human Immunodeficiency Virus Type 1 Nucleic Acid Sequences in Human Fetal DNA. AU - Soeiro, Ruy. AU - Rubinstein, Arye. AU - Rashbaum, William K.. AU - Lyman, William D.. PY - 1992/10. Y1 - 1992/10. N2 - Pediatric AIDS is increasing in frequency due to a rise in the number of human immunodeficiency virus type 1 (HIV-l)-infected women of childbearing age. Because outcome studies reveal that most children infected peripartum manifest HIV-1-related disease in the first year of life, intrauterine infection has been suspected. Fetal tissues from 23 second-trimester abortuses were examined. The presence of HIV-1 nucleic acid sequences was determined by the polymerase chain reaction and used to define infection of the fetus. By analysis of available tissues, 7 of 23 fetuses were infected, while control fetal tissue was negative. In situ hybridization for HIV-1 DNA showed that only 1 of 8 infected abortuses was positive, while all ...
Genetic polymorphisms in chemokine and chemokine receptor genes influence susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and disease progression, but little is known regarding the association between these allelic variations and the ability of the host to transmit virus. In this study, we show that the maternal heterozygous SDF1 genotype (SDF1 3A/wt) is associated with perinatal transmission of HIV-1 (risk ratio [RR], 1.8; 95% confidence interval [CI], 1.0 to 3.3) and particularly postnatal breastmilk transmission (RR, 3.1; 95% CI, 1.1 to 8.6). In contrast, the infant SDF1 genotype had no effect on mother-to-infant transmission. These data suggest that SDF1, which is a ligand for the T-tropic HIV-1 coreceptor CXCR4, may affect the ability of a mother to transmit the virus to her infant. This suggests that a genetic polymorphism in a gene encoding a chemokine receptor ligand may be associated with increased infectivity of the index case and highlights the importance of
TY - JOUR. T1 - Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro. AU - Yoon, Jong-Bok. AU - Li, Gen. AU - Roeder, Robert G.. PY - 1994/1/1. Y1 - 1994/1/1. N2 - LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box. We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box. Four similar but distinct cDNAs encoding LBP-1 (LBP-1a, -b, -c, and -d) have been isolated. These are products of two related genes, and each gene encodes two alternatively spliced products. Comparison of the amino acid sequence of LBP- 1 with entries in the available protein data bases revealed the identity of LBP-1c to α-CP2, an α-globin transcription factor. These proteins are also homologous to Drosophila melanogaster Elf-1/NTF-1, an essential transcriptional ...
709C.1 Criminal transmission of human immunodeficiency virus.. 1. A person commits criminal transmission of the human immunodeficiency virus if the person, knowing that the person s human immunodeficiency virus status is positive, does any of the following:. a. Engages in intimate contact with another person.. b. Transfers, donates, or provides the person s blood, tissue, semen, organs, or other potentially infectious bodily fluids for transfusion, transplantation, insemination, or other administration to another person.. c. Dispenses, delivers, exchanges, sells, or in any other way transfers to another person any nonsterile intravenous or intramuscular drug paraphernalia previously used by the person infected with the human immunodeficiency virus.. 2. For the purposes of this section:. a. Human immunodeficiency virus means the human immunodeficiency virus identified as the causative agent of acquired immune deficiency syndrome.. b. Intimate contact means the intentional exposure of the body of ...
TY - JOUR. T1 - Increased Mortality Associated With Vitamin A Deficiency During Human Immunodeficiency Virus Type 1 Infection. AU - Semba, Richard David. AU - Graham, Neil M H. AU - Caiaffa, Waleska T.. AU - Margolick, Joseph Bernard. AU - Clement, Liliana. AU - Vlahov, David. PY - 1993. Y1 - 1993. N2 - Objective: To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 (HIV-1) infection. Patients and Patients and Methods: Analysis of vitamin A levels, CD4 T cells, complete blood cell count, and serologic markers for liver disease in a random subsample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival. Results: Mean (±SE) follow-up time was 22.8±1.1 months, and 15 subjects died during follow-up. More than 15% of the HIV-l-seropositive individuals had plasma vitamin A levels less than 1.05 μmol/L, a level consistent with vitamin A ...
Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and
An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data ...
A panel of anti-gp120 human monoclonal antibodies (HuMAbs), CD4-IgG, and sera from people infected with human immunodeficiency virus type 1 (HIV-1) was tested for neutralization of nine primary HIV-1 isolates, one molecularly cloned primary strain (JR-CSF), and two strains (IIIB and MN) adapted for growth in transformed T-cell lines. All the viruses were grown in mitogen-stimulated peripheral blood mononuclear cells and were tested for their ability to infect these cells in the presence and absence of the reagents mentioned above. In general, the primary isolates were relatively resistant to neutralization by the MAbs tested, compared with the T-cell line-adapted strains. However, one HuMAb, IgG1b12, was able to neutralize most of the primary isolates at concentrations of | or = 1 microgram/ml. Usually, the inability of a HuMAb to neutralize a primary isolate was not due merely to the absence of the antibody epitope from the virus; the majority of the HuMAbs bound with high affinity to monomeric gp120
Three examples of human plasma-derived concentrates, intermediate-purity factors VIII and IX, and fibrinogen were spiked with tissue culture-grown human immunodeficiency virus type 1 (HIV-1) strain RF. All examples were freeze-dried and heated at 80 degrees C for 72 hours by using validated production process models. HIV-1 infectivity was measured by a syncytial infectivity assay in C8166 cells and then compared with levels determined by nested HIV polymerase chain reaction (PCR). The infectivity assay demonstrated a reduction index of at least 4.5 log10, while PCR showed an average 1.7 log10. Large amounts of HIV-1 RNA (10(5)) were still detectable by PCR in samples in which infectivity assays failed to detect any HIV-1. These data suggest that HIV-1 PCR levels do not parallel HIV-1 infectivity levels during virus-inactivation procedures involved in coagulation factor concentrate production. PCR was able to detect the RNA associated with inactivated HIV-1 particles in the factor concentrates, which
article{ff4f8a23-6ca4-4f67-9971-6842888c6b56, abstract = {Human immunodeficiency virus type-2 (HIV-2) infected individuals develop immunodeficiency with a considerable delay and transmit the virus at a lower rate as compared to HIV-1 infected. Conceivably, comparative studies on immune responsiveness of the HIV-1 and HIV-2 infected hosts may help to explain differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than HIV-1 infection. In the present study we have further examined the function of the humoral immune response and studied the potentiating effect of complement (C) on antiviral activity of plasma from singly HIV-1 or HIV-2 infected, as well as HIV-1/HIV-2 dually infected individuals. Neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4-CCR5 cells. Results ...
Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1
TY - JOUR. T1 - Molecular cloning of full-length HIV-1 genomes directly from plasma viral RNA. AU - Fang, Guowei. AU - Weiser, Barbara. AU - Visosky, Aloise A.. AU - Townsend, Laura. AU - Burger, Harold. PY - 1996. Y1 - 1996. N2 - Human immunodeficiency virus type 1 (HIV-1) in plasma reflects the replicating virus population at any point in time in vivo. Studies of the relationship of the complete HIV-1 genome to pathogenesis therefore need to focus on plasma virions. Since dual infections and recombination can occur in vivo, cloning an intact plasma virus genome as a single full-length molecule is desirable. For these reasons, we developed an efficient method to clone full-length HIV-1 genomes directly from plasma viral RNA. This method used reverse transcription and long polymerase chain reaction (PCR) amplification. Virion-associated RNA was isolated from plasma samples and then reverse- transcribed to make cDNA for PCR amplification. Two different strategies were employed to amplify the ...
Four glycoproteins of apparent molecular weights 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) are detectable in human immunodeficiency virus type 2 (HIV-2) infected cells. The gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. The gp300, which is a dimeric form of gp140, the precursor of HIV-2 envelope glycoprotein, is probably formed by a pH dependent fusion in the endoplasmic reticulum. Such a doublet is also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 does not form a dimer during its processing. Experiments carried out with various inhibitors of oligosaccharide trimming enzymes suggest that transient dimerization of the glycoprotein precursor is required for its efficient transport to the Golgi apparatus and for its processing. The gp300 is useful for detecting antibodies to
Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4+ target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1α, and MIP-1β, which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains. ...
Existing highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being actively pursued to eliminate the latent aspect of HIV-1 infection involves therapies combining latency antagonists with HAART. However, discordant pharmacokinetics between these types of drugs can potentially create sites of active viral replication within certain tissues that might be impervious to HAART. A preliminary reverse genetic screen indicated that the proteasome might be involved in the maintenance of the latent state. This prompted testing to determine the effects of proteasome inhibitors (PIs) on latently infected cells. Experiments demonstrated that PIs effectively activated latent HIV-1 in several model systems, including primary T cell models, thereby defining PIs as a new class of HIV-1
Combinations of reverse transcriptase (RT) inhibitors are currently used in anti-human immunodeficiency virus therapy in order to prevent or delay the emergence of resistant virus and to improve the efficacy against viral enzymes carrying resistance mutations. Drug-drug interactions can result in ei …
Clinical trial for Human Immunodeficiency Virus | Infection | HIV infection , Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
This invention is directed toward the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of AIDS, both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. However, preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1 positive sera. Overlapping molecular clones were obtained and the complete nucleotide sequence of the gag and env genes was ascertained. An antigenic envelope polypeptide having the following amino acid sequence was identified: NH2
Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8(+)- and CD4(+)-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8(+)-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8(+)-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative
Cervical and vaginal secretions from 17 women infected with human immunodeficiency virus type 1 (HIV-1) were evaluated daily through the course of one menstrual cycle for HIV-1 DNA (21-31 visits per woman). HIV-1-infected cells were detected in 207 (46%) of 450 endocervical swabs and 74 (16%) of 449 vaginal swabs. There was considerable variability in the percentage of positive swabs from each woman, ranging from 4% to 100% of endocervical swabs and from 0 to 71% of vaginal swabs. In multivariate analyses, plasma HIV-1 RNA was significantly associated with shedding of HIV-1-infected cells; each 1-unit increase in the log of plasma virus load was associated with a 5.6-fold increase in the odds of cervical shedding (95% confidence interval [CI], 2.1-14.8) and a 3.9-fold increase in the odds of vaginal shedding (95% CI, 2.1-7.2). There was no discernible pattern of genital tract shedding with phase of the menstrual cycle and no significant association with serum estradiol or progesterone levels ...
The cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1) was studied using MOLT-4 cells chronically infected with a variant strain of HIV-1SF-2 (MOLT-4/HIV-1SF-2H) and CD4+ human lymphoid MT-4 cells. MOLT-4/HIV-1SF-2H cells produced less than 1 TCID50 infectious particles per 105 cells per day as determined by the cytopathogenicity in MT-4 cells. However, the expression of envelope glycoproteins gp120 and gp41 on the MOLT-4/HIV-1SF-2H cell membrane was satisfactory for syncytium formation with the uninfected MOLT-4 cells. When MOLT-4/HIV-1SF-2H and MT-4 cells were co-cultured, severe cytopathogenicity was observed in MT-4 cells without being accompanied by the formation of multi-nucleated cells. Thus, the system consisting of MOLT-4/HIV-1SF-2H and MT-4 cells is convenient for exclusive study of the mechanism of cell-to-cell transmission of HIV-1. Using various compounds, it was confirmed that cell-to-cell transmission required both gp120/gp41-CD4 binding and de novo DNA ...
TY - JOUR. T1 - Factors associated with nucleic acids related to human immunodeficiency virus type 1 in cervico-vaginal secretions. AU - Spinillo, Arsenio. AU - Debiaggi, Maurizia. AU - Zara, Francesca. AU - Maserati, Renato. AU - Polatti, Franco. AU - De Santolo, Antonella. PY - 2001/6. Y1 - 2001/6. N2 - Objective: To assess HIV-related nucleic acids in cervico-vaginal secretions and the factors associated with them. Design: Observational study. Setting: Department of Obstetrics and Gynaecology, University of Pavia, Italy. Population: HIV-positive patients attending a cytology service. Methods: Paired blood and cervico-vaginal lavage samples were obtained from 122 known HIV-seropositive patients during periodic visits for cytologic screening for lower genital tract neoplasia. Vaginal specimens for the diagnosis of bacterial vaginosis, trichomonas vaginalis and candida infection were also obtained. HIV-1-RNA in plasma, proviral HIV-1-DNA, cell associated and cell-free HIV-1 RNA in ...
There is increasing evidence that CD8 lymphocytes may represent targets for infection by human immunodeficiency virus type 1 (HIV-1) in vivo whose destruction may contribute to the loss of immune function underlying AIDS. HIV-1 may infect thymic precursor cells destined to become CD4 and CD8 lymphocytes and contribute to the numerical decline in both subsets on disease progression. There is also evidence for the induction of CD4 expression and susceptibility to infection by HIV-1 of CD8 lymphocytes activated in vitro. To investigate the relationship between CD8 activation and infection by HIV-1 in vivo, activated subsets of CD8 lymphocytes in peripheral blood mononuclear cells (PBMCs) of HIV-seropositive individuals were investigated for CD4 expression and HIV infection. Activated CD8 lymphocytes were identified by expression of CD69, CD71, and the human leukocyte antigen (HLA) class II, the beta-chain of CD8, and the RO isoform of CD45. CD4(+) and CD4(-) CD8 lymphocytes, CD4 lymphocytes, other T cells,
HIV-2 was first described in 19851 and was isolated in 1986 in West Africa,2 where it is currently endemic. The Centers for Disease Control and Prevention (CDC) reported that, from 1988 to June 2010, 166 cases had met the CDC case definition of HIV-2 infection in the United States.3 The largest number of cases were from the Northeast, including 77 from New York City.3 The majority of cases had a West African origin or connection.3 However, a report from New York City suggests that HIV-2 may be underreported because antibody cross-reactivity between HIV-1 and HIV-2 is common and frequently results in misdiagnosis of HIV-2 as HIV-1 or dual infection.4 Incorporating a type-differentiating immunoassay into the HIV screening protocol can assist in identifying the type. ...
Abstract. Objective: To evaluate the impact of antiretroviral therapy (ART) on HIV-1 transmission rates among HIV-1 discordant couples in Rakai, Uganda.. Design: Observational cohort study.. Methods: HIV-1 discordant couples were retrospectively identified between 2004 and 2009. Study participants underwent annual screening for HIV-1 and were interviewed to evaluate risk behaviors. Participants were offered voluntary counseling and testing and provided with risk reduction counseling. Free ART was offered to participants with a CD4 cell count of 250 cells/μl or less or WHO stage IV disease. HIV-1 incidence and sexual risk behaviors were compared before and after the HIV-1-positive index partners started ART.. Results: Two hundred and fifty HIV-1 discordant couples were followed between 2004 and 2009 and 32 HIV-1-positive partners initiated ART. Forty-two HIV-1 transmissions occurred over 459.4 person-years prior to ART initiation, incidence 9.2/100 person-years [95% confidence interval (CI) ...
The HIV-1 regulatory proteins Rev and Tat are expressed early in the virus life cycle and thus may be important targets for the immune control of HIV-1-infection and for effective vaccines. However, the extent to which these proteins are targeted in natural HIV-1 infection as well as precise epitopes targeted by human cytotoxic T lymphocytes (CTL) remain to be defined. In the present study, 57 HIV-1-infected individuals were screened for responses against Tat and Rev by using overlapping peptides spanning the entire Tat and Rev proteins. CD8+ T cell responses against Tat and Rev were found in up to 19 and 37% of HIV-1-infected individuals, respectively, indicating that these regulatory proteins are important targets for HIV-1-specific CTL. Despite the small size of these proteins, multiple CTL epitopes were identified in each. These data indicate that Tat and Rev are frequently targeted by CTL in natural HIV-1 infection and may be important targets for HIV vaccines.
TY - JOUR. T1 - Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. AU - Shiu, Carlum. AU - Cunningham, Coleen K.. AU - Greenough, Thomas. AU - Muresan, Petronella. AU - Sanchez-Merino, Victor. AU - Carey, Vincent. AU - Jackson, Brooks. AU - Ziemniak, Carrie. AU - Fox, Lawrence. AU - Belzer, Marvin. AU - Ray, Stuart C.. AU - Luzuriaga, Katherine. AU - Persaud, Deborah. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/10. Y1 - 2009/10. N2 - In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of ,50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production ...
Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency. Charles R. Rinaldo Jr.,1,2,* Xiao-Li Huang,1 Zheng Fan,1 Joseph B. Margolick,3 Luann Borowski,1 Aki Hoji,1 Christine Kalinyak,1 Deborah K. McMahon,1,2 Sharon A. Riddler,1,2 William H. Hildebrand,4 Richard B. Day,1 and John W. Mellors1,2,5. Graduate School of Public Health1 and School of Medicine,2 University of Pittsburgh, and the Veterans Affairs Medical Center,5 Pittsburgh, Pennsylvania 15261; Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 212053; and University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731904. Received 17 December 1999/Accepted 29 January 2000. Journal of Virology, May 2000, p. 4127-4138, Vol. 74, No. 9. The long-term efficacy of combination antiretroviral therapy may relate to augmentation of anti-human immunodeficiency virus type 1 (HIV-1) CD8+ T-cell ...
TY - JOUR. T1 - Human immunodeficiency virus type 1 enters brain microvascular endothelia by macropinocytosis dependent on lipid rafts and the mitogen-activated protein kinase signaling pathway. AU - Liu, Nancy Q.. AU - Lossinsky, Albert S.. AU - Popik, Waldemar. AU - Li, Xia. AU - Gujuluva, Chandrasekhar. AU - Kriederman, Benjamin. AU - Roberts, Jaclyn. AU - Pushkarsky, Tatania. AU - Bukrinsky, Michael. AU - Witte, Marlys. AU - Weinand, Martin. AU - Fiala, Milan. PY - 2002/6/25. Y1 - 2002/6/25. N2 - Brain microvascular endothelial cells (BMVECs) present an incomplete barrier to human immunodeficiency virus type 1 (HIV-1) neuroinvasion. In order to clarify the mechanisms of HIV-1 invasion, we have examined HIV-1 uptake and transcellular penetration in an in vitro BMVEC model. No evidence of productive infection was observed by luciferase, PCR, and reverse transcriptase assays. Approximately 1% of viral RNA and 1% of infectious virus penetrated the BMVEC barrier without disruption of tight ...
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
Fingerprint Dive into the research topics of Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis. Together they form a unique fingerprint. ...
TY - JOUR. T1 - Maternal viral genotypic zidovudine resistance and infrequent failure of zidovudine therapy to prevent perinatal transmission of human immunodeficiency virus type 1 in Pediatric AIDS Clinical Trials Group protocol 076. AU - Eastman, P. Scott. AU - Shapiro, David E.. AU - Coombs, Robert W.. AU - Frenkel, Lisa M.. AU - McSherry, George D.. AU - Britto, Paula. AU - Herman, Steven A.. AU - Sperling, Rhoda S.. PY - 1998. Y1 - 1998. N2 - Maternal samples were assessed from 96 women enrolled in Pediatric AIDS Clinical Trials Group protocol 076 to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) genotypic zidovudine resistance at entry, if zidovudine resistance developed on study, and the role of zidovudine resistance in vertical transmission of HIV-1 despite zidovudine therapy. Low and high levels of genotypic resistance were assessed by differential hybridization, oligoligation, or direct sequencing of plasma HIV-1 RNA for codons K70R and T215Y/F. None of the ...
TY - JOUR. T1 - Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1- infected long-term survivors. AU - Betts, Michael R.. AU - Krowka, John F.. AU - Kepler, Thomas B.. AU - Davidian, Marie. AU - Christopherson, Cindy. AU - Kwok, Shirley. AU - Louie, Leslie. AU - Eron, Joseph. AU - Sheppard, Haynes. AU - Frelinger, Jeffrey A.. PY - 1999/9/1. Y1 - 1999/9/1. N2 - HIV-1-specific cytotoxic T cell (CTL) activity has been suggested to correlate with protection from progression to AIDS. We have examined the relationship between HIV-specific CTL activity and maintenance of peripheral blood CD4+ T lymphocyte counts and control of viral load in 17 long-term survivors (LTSs) of HIV-1 infection. Longitudinal analysis indicated that the LTS cohort demonstrated a decreased rate of CD4+ T cell loss (18 cells/mm3/year) compared with typical normal progressors (approximately 60 cells/mm3/year). The majority of the LTSs had ...
TY - JOUR. T1 - Human cytomegalovirus and human immunodeficiency virus type-1 co-infection in human cervical tissue. AU - Fox-Canale, Andrea M.. AU - Hope, Thomas J.. AU - Martinson, Jeffrey. AU - Lurain, John R.. AU - Rademaker, Alfred W.. AU - Bremer, James W.. AU - Landay, Alan. AU - Spear, Gregory T.. AU - Lurain, Nell S.. PY - 2007/12/5. Y1 - 2007/12/5. N2 - Human cytomegalovirus (HCMV) and human immunodeficiency virus type-1 (HIV-1) infect the female genital tract. A human cervical explant model was developed to study single and dual infection by these viruses in the genital compartment. An HCMV strain expressing green fluorescent protein, and two clinical HCMV strains produced peak viral DNA copies at 14 to 21 days post-infection. Peak levels of HIV-1Ba-L p24 antigen occurred at 7 days post-infection. HIV-1Ba-L appeared to enhance HCMV in co-infected tissues. Singly and dually infected explants produced increased levels of cytokines IL-6, IL-8, and GRO-α in culture supernatants. ...
Glutamine is a conditionally essential amino acid that is an important metabolic resource for proliferating tissues by acting as a proteinogenic amino acid, a nitrogen donor for biosynthetic reactions and as a substrate for the citric acid or tricarboxylic acid cycle. The human immunodeficiency virus type 1 (HIV-1) productively infects activated CD4(+) T cells that are known to require glutamine for proliferation and for carrying out effector functions. As a virus, HIV-1 is furthermore entirely dependent on host metabolism to support its replication. In this study, we compared HIV-1 infected with uninfected activated primary human CD4(+) T cells with regard to glutamine metabolism. We report that glutamine concentrations are elevated in HIV-1-infected cells and that glutamine is important to support HIV-1 replication, although the latter is closely linked to the glutamine dependency of cell survival. Metabolic tracer experiments showed that entry of glutamine-derived carbon into the citric acid ...
Background. the genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades.Methods. Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon-gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous ( infecting) clades of HIV-1.Results. Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade ...
A human immunodeficiency virus type 2 (HIV-2)-infected woman experienced asymptomatic superinfection with HIV-1 subtype AG. She did not have cross-neutralizing autologous HIV-1 antibodies before and shortly after HIV-1 superinfection. This evidence supports a mechanism other than cross-neutralizing antibodies for the mild course of HIV-1 infection in this woman.. ...
HIV-1-particular antibody-dependent cellular cytotoxicity (ADCC) antibodies within HIV-1-positive (HIV-1+) individuals predominantly target CD4-induced (CD4i) epitopes on HIV-1 envelope glycoprotein (Env). various stages of downregulating CD4, were all susceptible to NK cell-mediated ADCC. Importantly, we PCDH9 observed that this cytolysis of bystander cells and early infected cells in this culture system was driven by sensitization of target cells by inoculum-derived HIV-1 Env or virions. This phenomenon provided Env to target cells prior to Env expression, resulting in artifactual ADCC measurements. Future studies should take into consideration the inherent caveats of contamination systems and develop improved models to address the potential role for ADCC against cells with nascent HIV-1 contamination. IMPORTANCE An increasing body of evidence suggests that ADCC contributes to protection against HIV-1 acquisition and slower HIV-1 disease progression. Targeting cells early through the infection ...
HIV-2 was first described in 1985 in West Africa on the basis of its antigenic relationship to HIV-1 and the SIV [1,2]. Since that time, several international research collaborations have sought to understand the pathogenicity of this closely related HIV virus and the impact of its interaction with the prototype HIV-1 infection in vivo. Coexisting in West Africa with HIV-1, HIV-2, by contrast generally demonstrates an attenuated phenotype for transmission and disease [3,4]. In rural Guinea Bissau, a more bimodal outcome has been described with HIV-2 progressors indistinguishable from HIV-1 progressors, and HIV-2 controllers (35-40%) maintaining undetectable viral load for 10-15 years, with a normal life expectancy [5]. In 1995, the concept that HIV-2 might protect from HIV-1 infection was raised from long-term studies of the registered sex worker cohort in Dakar, Senegal [6,7]. The generalizability of these findings was questioned by studies from Ivory Coast, Guinea Bissau and the Gambia [8-10]. ...
The vertical transmission of the Human Immunodeficiency Virus Type 1 (HIV -1) is defined as the transmission of the virus from infected mother to fetus. In order to infect the fetal blood supply in utero, the virus must pass through the placenta. The virus collects in the placental trophoblast, and only certain strains are able to pass from that point into the fetal blood supply, because the placental trophoblast is not a strong host for HIV replication. This report analyzes transcription factors present in placental trophoblast which may be critically important to HIV replication in trophoblast. This is done through the use of a set of 27 linker-scanning mutants created by Dr. Steven L. Zeichner in Philadelphia. These mutants replace 18 bp at a time in subsequent order along the U3 and R regions of the viral long terminal repeat (LTR). The U3 and R regions of the LTR are primarily regions of viral transcriptional control. By transfecting the mutated LTRs into human placental trophoblasts, it ...
Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3,3-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag.
We have investigated the molecular basis of biological differences observed among cell line-adapted isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and the simian immunodeficiency virus (SIV) in response to receptor binding by using a soluble form of CD4 (sCD4) as a receptor mimic. We find that sCD4 binds to the envelope glycoproteins of all of the HIV-1 isolates tested with affinities within a threefold range, whereas those of the HIV-2 and SIV isolates have relative affinities for sCD4 two- to eightfold lower than those of HIV-1. Treatment of infected cells with sCD4 induced the dissociation of gp120 from gp41 and increased the exposure of a cryptic gp41 epitope on all of the HIV-1 isolates. By contrast, neither dissociation of the outer envelope glycoprotein nor increased exposure of the transmembrane glycoprotein was observed when sCD4 bound to HIV-2- or SIV-infected cells. Moreover, immunoprecipitation with sCD4 resulted in the coprecipitation of the surface and
In Guinea-Bissau HIV-1, HIV-2, and HTLV-I are prevalent in the general population. The natural history of HIV/HTLV-I single and dual infections has not been fully elucidated in this population. Previous studies have shown that combinations of these infections are more common in older women than in men. The present study compares mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in individuals over 35 years of age within an urban community-based cohort in Guinea-Bissau. A total of 2,839 and 1,075 individuals were included in the HIV and HTLV-I mortality analyses respectively. Compared with HIV-negative individuals, adjusted mortality rate ratios (MRRs) were 4.9 (95% confidence interval (CI): 2.3, 10.4) for HIV-1, 1.8 (95%CI: 1.5, 2.3) for HIV-2, and 5.9 (2.4, 14.3) for HIV-1/HIV-2 dual infections. MRR for HTLV-I-positive compared with HTLV-I-negative individuals was 1.7 (1.1, 2.7). Excluding all HIV-positive individuals from the analysis, the HTLV-I MRR was 2.3 (1.3, 3.8). The
During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia during the course of donations; HIV-1-positive individuals progressing from early to chronic infection; and chronically HIV-1-infected individuals (receiving antiretroviral therapy or untreated). Hepcidin increased and plasma iron decreased during acute HIV-1 infection, as viremia was initially detected. In patients transitioning from early to chronic HIV-1 infection, hepcidin in the first 60 d of infection positively correlated with the later plasma viral load set-point. Hepcidin remained elevated in individuals with untreated chronic HIV-1 infection and in subjects on ART. In contrast to HIV-1, there was no evidence of hepcidin ...
Objectives: Rapid human immunodeficiency virus (HIV) antibody tests, routinely used for diagnosis in adults and older children in resource-limited settings (RLS), do not detect early HIV infections prior to seroconversion or when antibody levels are still low. Nucleic acid amplification to detect HIV-1 RNA is the most sensitive method for acute HIV infection diagnosis, but is costly. We therefore investigated HIV- 1 RNA testing of pooled dried blood spots (DBS) to diagnose acute HIV infection. Design: Laboratory-based investigation. Methods: DBS were collected from HIV-1 Voluntary Counselling and Testing (HVCT) clients who tested negative on the Advanced QualityTM HIV antibody rapid test. DBS samples from five participants were pooled and tested on the COBAS AmpliPrep/COBAS TaqMan HIV-1 (CAP/CTM) Test v2. Individual DBS were tested when pools tested positive (, 200 RNA copies/ml). Acute infection was confirmed by HIV viral load testing, two fourth-generation HIV serological assays, and ...
Background The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated.. Methods The effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-kB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation.. Results The results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription. CMTM2 exerted a ...
CONTEXT: Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting.. OBJECTIVE: To evaluate the association of preexisting drug-resistant HIV-1 minority variants with risk of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral virologic failure.. DATA SOURCES: Systematic review of published and unpublished studies in PubMed (1966 through December 2010), EMBASE (1974 through December 2010), conference abstracts, and article references. Authors of all studies were contacted for detailed laboratory, ART, and adherence data.. STUDY SELECTION AND DATA ABSTRACTION: Studies involving ART-naive participants initiating NNRTI-based regimens were included. Participants were included if all drugs in their ART regimen were fully active by standard HIV ...
Other Development of an effective low-cost anti-acquired immunodeficiency syndrome (AIDS) drugs is needed for treatment of AIDS patients in developing countries. Host cell lipid raft microdomains, which are enriched with cholesterol, glycolipids, ceramide, and gangliosides, are important for human immunodeficiency virus type 1 (HIV-1) entry. Retinoid analogs have been shown to modulate ceramide levels in the cell membrane, while cholera toxin B subunit (CT-B) specifically binds to the ganglioside GM1. In this study, we found that the acyclic retinoid analogs geranylgeranoic acid (GGA) and NIK-333 as well as CT-B efficiently attenuate CXCR4-tropic, but not CCR5-tropic, HIV-1 vector infection. We also found that GGA and NIK-333 suppress CXCR4-tropic HIV-1 infection by attenuating CXCR4 expression. CT-B also attenuated CXCR4-tropic HIV-1 infection, but did not suppress CXCR4 expression. These results suggest a distinct role for lipid raft microdomains in CXCR4- and CCR5-tropic HIV-1 infections and ...
Lien vers Pubmed [PMID] - 15218022. J. Biol. Chem. 2004 Aug;279(35):36625-32. By frequently rearranging large regions of the genome, genetic recombination is a major determinant in the plasticity of the human immunodeficiency virus type I (HIV-1) population. In retroviruses, recombination mostly occurs by template switching during reverse transcription. The generation of retroviral vectors provides a means to study this process after a single cycle of infection of cells in culture. Using HIV-1-derived vectors, we present here the first characterization and estimate of the strength of a recombination hot spot in HIV-1 in vivo. In the hot spot region, located within the C2 portion of the gp120 envelope gene, the rate of recombination is up to ten times higher than in the surrounding regions. The hot region corresponds to a previously identified RNA hairpin structure. Although recombination breakpoints in vivo cluster in the top portion of the hairpin, the bias for template switching in this same ...
TY - JOUR. T1 - Effect of HIV-1 Tat on Secretion of TNF-α and IL-1β by U87 Cells in AIDS Patients with or without AIDS Dementia Complex. AU - Zhao, Li. AU - Pu, Shuang Shuang. AU - Gao, Wen Hua. AU - Chi, Yuan Yuan. AU - Wen, Hong Ling. AU - Wang, Zhi Yu. AU - Song, Yan Yan. AU - Yu, Xue Jie. PY - 2014/2. Y1 - 2014/2. N2 - Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of ...
TY - JOUR. T1 - HIV-1, HIV-2, and HTLV-I Infection in High-Risk Groups in Brazil. AU - Cortes, Eduardo. AU - Detels, Roger. AU - Aboulafia, David. AU - li, Xi Ling. AU - Moudgil, Tarsem. AU - Alam, Masud. AU - Bonecker, Carlos. AU - Gonzaga, Augusto. AU - Oyafuso, Luiza. AU - Tondo, Michele. AU - Boite, Carlos. AU - Hammershlak, Nelson. AU - Capitani, Carlos. AU - Slamon, Dennis J.. AU - ho, David D.. PY - 1989/4/13. Y1 - 1989/4/13. N2 - We conducted a serologic survey for antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and human T-cell lymphotropic virus Type I (HTLV-I) in 704 Brazilians with the acquired immunodeficiency syndrome (AIDS) or at risk for it. The study population included 70 homosexual men (11 of whom were prostitutes), 58 bisexual men (19 of whom were prostitutes), 101 female prostitutes from three socioeconomic groups, 13 wives of men with hemophilia who were seropositive for HIV-1 antibodies, and 47 blood donors with positive Venereal Disease Research ...
21948 there is some evidence that infection with human immunodeficiency virus (HIV) may be a factor in the development or worsening of the condition under consideration.. 2464 the veteran has been infected with the human immunodeficiency virus (HIV).. 28120 the veteran has established the causal connection between the infection with HIV and VEA service for the condition under consideration.. 28121 the veteran was infected with human immunodeficiency virus (HIV) at the time of the clinical onset of the condition under consideration.. 28122 the veteran has established the causal connection between the infection with HIV and VEA service for the clinical onset of the condition under consideration.. 28125 the veteran has established the causal connection between the infection with HIV and operational service for the clinical onset of the condition under consideration.. or. 28126 the veteran has established the causal connection between the infection with HIV and eligible service for the clinical ...
Cell-cell interactions through direct contact are very important for cellular communication and coordination especially for immune cells. The human immunodeficiency virus type I (HIV-1) induces immune cell interactions between CD4(+) cells to shuttle between T cells via a virological synapse. A goal to understand the process of cell-cell transmission through virological synapses is to determine the cellular states that allow a chance encounter between cells to become a stable cell-cell adhesion. We demonstrate the use of optical tweezers to manipulate uninfected primary CD4(+) T cells near HIV Gag-iGFP transfected Jurkat T cells to probe the determinants that induce stable adhesion. When combined with fast 4D confocal fluorescence microscopy, optical tweezers can be utilized not only to facilitate cell-cell contact, but also to simultaneously track the formation of a virological synapse, and ultimately to probe the events that precede virus transfer. [GRAPHICS] HIV-1 infected T cell (green) ...
Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging
Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity).
The prevalence of the CCR2b-V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b-V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4(+) T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b-V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b-V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log(10) ...
Despite great progress in the treatment of AIDS, the Human Immunodeficiency Virus type I (HIV-1) remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In this paper we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. Based on the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment can not be inferred solely from the results of the in vitro experiments. ...
The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines.. ...
TY - JOUR. T1 - HIV-1 Vpr Accelerates Viral Replication during Acute Infection by Exploitation of Proliferating CD4+ T Cells In Vivo. AU - Sato, Kei. AU - Misawa, Naoko. AU - Iwami, Shingo. AU - Satou, Yorifumi. AU - Matsuoka, Masao. AU - Ishizaka, Yukihito. AU - Ito, Mamoru. AU - Aihara, Kazuyuki. AU - An, Dong Sung. AU - Koyanagi, Yoshio. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2013. Y1 - 2013. N2 - The precise role of viral protein R (Vpr), an HIV-1-encoded protein, during HIV-1 infection and its contribution to the development of AIDS remain unclear. Previous reports have shown that Vpr has the ability to cause G2 cell cycle arrest and apoptosis in HIV-1-infected cells in vitro. In addition, vpr is highly conserved in transmitted/founder HIV-1s and in all primate lentiviruses, which are evolutionarily related to HIV-1. Although these findings suggest an important role of Vpr in HIV-1 pathogenesis, its direct evidence in vivo has not been shown. Here, by using ...
Three types of antiretroviral drugs (ARVs) are now used for the treatment of human immunodeficiency virus type 1 (HIV-1) infections, but only reverse transcriptase (RT) inhibitors are readily available to the vast majority of HIV-1-infected individuals in the developing world. The treatment regimen of choice is a combination of a nonnucleoside RT inhibitor (almost exclusively nevirapine [NVP]) and two nucleoside RT inhibitors, i.e., zidovudine (AZT) or stavudine plus lamivudine or didanosine.. In addition to being the backbone of most treatment regimens, NVP is provided as a single dose to block the mother-to-child transmission (MTCT) of HIV-1 in developing countries. In the absence of antiretroviral therapy, the frequency of MTCT is approximately 25 to 48% (2, 36, 38), whereas the administration of a short course of AZT therapy near the end of gestation (7, 8, 49) or the administration of a single dose of NVP at labor can reduce the rate of perinatal transmission to less than 20% (22, 25, 32, ...
In human immunodeficiency virus (HIV)-infected individuals, the proportion of circulating mononuclear cells (PBMCs) which carry HIV provirus and the number of HIV proviral sequences per infected PBMC have been matters for conjecture. Using a double polymerase chain reaction which allows the detection of single molecules of provirus and a method of quantifying the provirus molecules, we have measured provirus frequencies in infected individuals down to a level of one molecule per 10(6) PBMCs. As a general rule, only a small proportion of PBMCs contain provirus (median value of samples from 12 patients, one per 8,000 cells), and most if not all of the infected cells carry a single provirus molecule. The frequency of provirus-carrying cells correlated positively both with the progression of the disease and with the success with which virus could be isolated from the same patients by cocultivation methods. Of seven asymptomatic (Centers for Disease Control stage II) patients, all but one contained one
Residual viral replication persists in a significant proportion of human immunodeficiency virus (HIV)-infected patients receiving potent antiretroviral therapy. To determine the source of this virus, levels of HIV RNA and DNA from lymphoid tissues and levels of viral RNA in serum, cerebrospinal fluid (CSF), and genital secretions in 28 patients treated for ⩽2.5 years with indinavir, zidovudine, and lamivudine were examined. Both HIV RNA and DNA remained detectable in all lymph nodes. In contrast, HIV RNA was not detected in 20 of 23 genital secretions or in any of 13 CSF samples after 2 years of treatment. HIV envelope sequence data from plasma and lymph nodes from 4 patients demonstrated sequence divergence, which suggests varying degrees of residual viral replication in 3 and absence in 1 patient. In patients receiving potent antiretroviral therapy, the greatest virus burden may continue to be in lymphoid tissues rather than in central nervous system or genitourinary compartments ...