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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Vpu protein is a human immunodeficiency virus type 1 (HIV-1)-specific accessory protein that is required for the efficient release of viral particles from infected cells. Even though HIV-2 does not encode Vpu, we found that this virus is nevertheless capable of efficiently releasing virus particles. In fact, the rate of virus release from HeLa cells transfected with a full-length molecular clone of HIV-2, ROD10, was comparable to that observed for the vpu+ HIV-1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans. However, consistent with previous observations showing that HIV-2 particle release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs; exchanging the gag-pol region of NL4-3 with the corresponding region from pROD10 rendered the resulting chimeric virus Vpu responsive. Our finding that the responsiveness of HIV-2 particle release to Vpu is context dependent suggested the presence of a Vpu-like factor(s) encoded by HIV-2. Using chimeric proviruses encoding HIV-2 gag and pol in the context of the HIV-1 provirus that were coexpressed with subgenomic HIV-2 constructs, we found that the HIV-2 envelope glycoprotein had the ability to enhance HIV-2 particle release with an efficiency comparable to that of the HIV-1 Vpu protein. Conversely, inactivation of the HIV-2 env gene in the original ROD10 clone resulted in a decrease in the rate of viral particle release to a level that was comparable to that of Vpu-deficient HIV-1 isolates. Providing the wild-type envelope in trans rescued the particle release defect of the ROD10 envelope mutant. Thus, unlike HIV-1, which encodes two separate proteins to regulate virus release or to mediate viral entry, the HIV-2 Env protein has evolved to perform both functions.
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PMID:The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral particle release: a Vpu-like factor? 855 20

We previously reported that expression of human immunodeficiency virus type 1 strain NL4-3 (HIV-1(NL4-3))vpr causes cells to arrest in the G2 phase of the cell cycle. We examined the induction of cell cycle arrest by other HIV-1 isolates and by primary lentiviruses other than HIV-1. We demonstrate that the vpr genes from tissue culture-adapted or primary isolates of HIV-1 are capable of inducing G2 arrest. In addition, we demonstrate that induction of cell cycle arrest is a conserved function of members of two other groups of primate lentiviruses, HIV-2/simian immunodeficiency virus strain sm (SIVsm)/SIVmac and SIVagm. vpr from HIV-1, HIV-2, and SIVmac induced cell cycle arrest when transfected in human (HeLa) and monkey (CV-1) cells. vpx from HIV-2 and SIVmac did not induce detectable cell cycle arrest in either cell type, and SIVagm vpx was capable of inducing arrest in CV-1 but not HeLa cells. These results indicate that induction of cell cycle perturbation is a general property of lentiviruses that infect primates. The conservation of this viral function throughout evolution suggests that it plays a key role in virus-host relationships, and elucidation of its mechanism may reveal important clues about pathology induced by primary lentiviruses.
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PMID:Vpr-induced cell cycle arrest is conserved among primate lentiviruses. 864 81

The nef genes of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) encode a 27- to 34-kDa myristoylated protein which induces downregulation of CD4 surface levels and enhances virus infectivity. In adult macaques, Nef has been implicated in pathogenesis and disease progression. Both HIV-1 SF2 Nef and SIVmac239 Nef have been shown to associate with a cellular serine/threonine kinase. We tested five functional Nef isolates to examine whether this kinase association is a property conserved among different isolates. HIV-1 SF2 and 248 and SIVmac239 Nef proteins were found associated with the kinase. HIV-1 NL4-3 and 233 Nef proteins were found weakly associated or not associated with the kinase. All five Nef isolates efficiently downregulated CD4 cell surface expression, suggesting that the association with this cellular kinase is not required for Nef to downregulate CD4. Comparison of the SF2 and NL4-3 isolates shows a differential ability of Nef to enhance infectivity that suggests a possible correlation between kinase association and enhancement of infectivity.
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PMID:The association of Nef with a cellular serine/threonine kinase and its enhancement of infectivity are viral isolate dependent. 870 88

A cell clone (Hut-78/F12) chronically infected with a non-producer human immunodeficiency virus type 1 (HIV-1) variant showed an abnormal pattern of virus structural proteins and released no detectable virus particles. Exchanges of homologous parts of the F12/HIV provirus and a replication-competent HIV (strain NL4-3) were undertaken to define the genetic determinants of the F12/HIV phenotype. The non-infectious phenotype was reproduced by replacing an NL4-3 genomic fragment encoding the C terminus of gp 120 and the N terminus of gp41 with the corresponding parts of the F12/HIV provirus. Conversely, a much more extended genomic fragment (encompassing the vif, pol and env genes) was necessary to convert the F12/HIV phenotype. These results demonstrate that the F12/HIV non-producer phenotype is the result of mutations scattered along most of the genome, rendering the conversion to an infectious phenotype a very unlikely event. The F12/HIV genome is thus a reliable model for preclinical studies of anti-HIV gene therapy.
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PMID:The non-producer phenotype of the human immunodeficiency virus type 1 provirus F12/HIV-1 is the result of multiple genetic variations. 881 Sep 97

We characterized in detail the life cycle of human immunodeficiency virus type 1 (HIV-1) in human glioma H4/CD4 cells which stably express transfected CD4 DNA (B. Volsky, K. Sakai, M. Reddy, and D. J. Volsky, Virology 186:303-308, 1992). Infection of cloned H4/CD4 cells with the N1T strain of cell-free HIV-1 (HIV-1/N1T) was rapid and highly productive as measured by the initial expression of viral DNA, RNA, and protein, but all viral products declined to low levels by 14 days after infection. Chronically infected, virus-producing H4/CD4 cells could be obtained by cell cloning, indicating that HIV-1 DNA can integrate and remain expressed in these cells. The HIV-1 produced in H4/CD4 cells was noninfectious to glial cells, but it could be transmitted with low efficiency to CEM cells. Examination of viral protein composition by immunoprecipitation with AIDS serum or anti-gp120 antibody revealed that HIV-1/N1T-infected H4/CD4 cells produced all major viral proteins including gp160, but not gp120. Deglycosylation experiments with three different glycosidases determined that the absence of gp120 was not due to aberrant glycosylation of gp160, indicating a defect in gp160 proteolytic processing. Similar results were obtained in acutely and chronically infected H4/CD4 cells. To determine the generality of this HIV-1 replication phenotype in H4/CD4 cells, nine different viral clones were tested for replication in H4/CD4 cells by transfection. Eight were transiently productive like N1T, but one clone, NL4-3, established a long-lived productive infection in H4/CD4 cells, produced infectious progeny virus, and produced both gp160 and gp120. We conclude that for most HIV-1 strains tested, HIV-1 infection of H4/CD4 is restricted to a single cycle because of the defective processing of gp160, resulting in the absence of gp120 on progeny virus.
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PMID:A mechanism of restricted human immunodeficiency virus type 1 expression in human glial cells. 889 23

Osteoblastic cells are in direct or indirect contact with lymphocytes and bone marrow cells that are the main targets of HIV-1. Therefore we analysed whether HIV-1 could infect these cells using three bone cell lines (HOS, MG-63, U2 OS) as a model. These cells were infected with HIV-1 (strain NL4-3) and the supernatants were harvested every day for 20 days for p24 antigen measured using an ELISA immunoassay. The DNA of infected cells was extracted at days 3, 9, and 12 and the PCR for gag gene was performed using Jurkat cell line as a negative control and ACH-2 cell line as a positive control. Our results demonstrated that HOS, MG-63 and U2 OS are not infected by HIV-1. These data were confirmed using PCR that is currently the most sensitive procedure available.
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PMID:Osteoblastic cell lines are not susceptible to HIV-1 infection. 896 98

We have recently shown that the envelope glycoprotein of the ROD10 isolate of human immunodeficiency virus type 2 (HIV-2) has the ability to positively regulate HIV-2 viral particle release. The activity provided by the ROD10 Env was remarkably similar to that of the HIV-1 Vpu protein, thus raising the possibility that the two proteins act in a related fashion. We now show that the ROD10 Env can functionally replace Vpu to enhance the rate of HIV-1 particle release. When provided in trans, both Vpu and the ROD10 Env restored wild-type levels of particle release in a Vpu-deficient mutant of the NL4-3 molecular clone with indistinguishable efficiencies. This effect was independent of the presence of the HIV-1 envelope protein. The ROD10 Env also enhanced HIV-1 particle release in the context of HIV-2 chimeric viruses containing the HIV-1 gag-pol, indicating a lack of need for additional HIV-1 products in this process. In addition, we show for the first time that HIV-1 Vpu, as well as ROD10 Env, has the ability to enhance simian immunodeficiency virus (SIV) particle release. The effects of Vpu and ROD10 Env on SIV particle release were indistinguishable and were observed in the context of full-length SIVmac239 and simian-human immunodeficiency virus chimeras. These results further demonstrate that ROD10 Env can functionally complement Vpu with respect to virus release. In contrast, we found no evidence of a destabilizing activity of ROD10 Env on the CD4 molecule. HIV-1 and HIV-2 thus appear to have evolved genetically distinct but functionally similar strategies to resolve the common problem of efficient release of progeny virus from infected cells.
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PMID:The human immunodeficiency virus (HIV) type 2 envelope protein is a functional complement to HIV type 1 Vpu that enhances particle release of heterologous retroviruses. 897 Sep 48

The effects on immunotoxin efficacy of fusogenic peptides derived from influenza virus hemagglutinin have been studied. These peptides have an amphipathic nature and change conformation from random at pH 7 to helical at pH 5. Fusogenic peptides are reported to destabilize endosomal membranes, resulting in the release of contents into the cytoplasm. The use of two related fusogenic peptides to enhance the efficacy of anti-HIV immunotoxins is described. The direct toxicity of the peptides was tested on HIV-infected H9/NL4-3 cells. Peptide HA24 was considerably more toxic than HA23. The peptides were mixed with two different immunotoxins. Immunotoxin action was enhanced by both peptides, with HA24 providing greater enhancement than HA23. Immunotoxins were then constructed by coupling HA23 or HA24 to the targeting antibody with disulfide-containing linkers. Peptide HA23 enhanced the activity of the immunotoxin 4-5-fold. Surprisingly, HA24 significantly inhibited immunotoxin activity. Coupling the peptides to the immunotoxin had no effect on antigen binding characteristics or the activity of the toxic moiety. Bafilomycin A1, an agent that inhibits vacuolar acidification, markedly potentiated the effects of all immunotoxins. These results demonstrate that amphipathic peptides can influence the efficacy of immunotoxins, but in sometimes unpredictable ways.
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PMID:Influence of endosome-destabilizing peptides on efficacy of anti-HIV immunotoxins. 902 33

The ability of HIV-1 to establish an infection and replicate to high copy number in CD4 lymphocytes is dependent on both the activation state of the cell and virus-encoded regulatory proteins that modulate viral gene expression. To study these required virus-cell interactions, we have used an in vitro cell model of acute HIV infection of quiescent, primary CD4 lymphocytes and subsequent induction of T cell activation and virus replication by lectin or CD3 receptor cross-linking. Experiments were done to determine if the capacity of HIV to establish infection and complete replication was impacted by the maturational state of the CD4 cell target or the specific signal induction pathway engaged during activation. Primary CD4 cells were FACS-sorted into the major phenotypic subsets representative of memory (CD45RO) and naive (CD45RA) cells. Levels of virus replication were compared between infection with wild-type NL4-3 virus and an isogenic mutant containing a deletion in nef regulatory gene. PHA mitogen stimulation was compared with anti-CD3, with and without anti-CD28 costimulation, for induction of cell proliferation and virus replication. In both infected and uninfected cells, the RA cell subset exhibited significantly greater response to CD3/CD28 stimulation than did the RO cell subset. In contrast, the majority of virus replication occurred consistently in the RO cell subset. Deletion of HIV nef function caused a severe reduction in viral replication, especially in the RA naive cell subset after CD3 induction. PCR analysis of viral DNA formation, during infection of quiescent cells, demonstrated that the observed differences in HIV replication capacity between RO and RA cell subsets were not due to inherent differences in cell susceptibility to infection. Our results indicate that HIV replication is enhanced selectively in CD45RO memory phenotype cells through the probable contribution of specialized cellular factors which are produced during CD3-initiated signal transduction.
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PMID:Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro. 912 23

Seven envelope regions from two series of patient isolates have been molecularly cloned and analyzed for replication phenotypes and immunogenicity. Growth potential was analyzed for env sequences substituted into an HIV-1-NL4-3 backbone (NL4-3/env recombinants). Immunogenicity studies were conducted on secreted monomeric (gp120) and oligomeric (gp140) forms of the Envs using Env-expressing plasmid DNAs for immunizations. The env regions of the patient isolates conferred a spectrum of replication kinetics and cytotropisms on the NL4-3/env recombinants. Both patient series included non-syncytium-inducing viruses with no ability to grow on T-cell lines, and highly syncytium inducing viruses which grew well on T-cell lines. These differences in growth potential did not correlate with the ability of the DNA-expressed Envs to raise antibody in rabbits. Rather, the relative immunogenicity of the Envs was patient and form specific. The Envs from patient 5 raised higher titers of antibody than the Envs from patient 6. For each primary Env, the gp120 form of the Env raised higher titers of antibody than the gp140 form. Thus, structural features of Env that affect replication do not necessarily affect the ability to raise antibody.
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PMID:HIV-1 Env glycoproteins from two series of primary isolates: replication phenotype and immunogenicity. 912 70


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