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

To study the intracellular transport and biological properties of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein (TM; gp41), we constructed a truncated envelope gene in which the majority of the coding sequences for the surface glycoprotein (SU; gp120) were deleted. Transient expression of this truncated env gene in primate cells resulted in the biosynthesis of two proteins with M(r)s of 52,000 and 41,000, respectively. Immunofluorescence studies with antibodies to the HIV-1 TM protein indicated that the intracellular and surface localization of these proteins were indistinguishable from those of the native HIV-1 gp120-gp41 complex. These results indicate that the oligosaccharide processing and cell surface transport of the HIV-1 TM protein were not dependent on the presence of the receptor binding subunit, gp120. Syncytium formation was readily detected upon expression of the deleted HIV-1 env gene into COS and CD4+ HeLa cell lines, suggesting that in the absence of gp120, the TM protein retained biological activity. This observation was confirmed by infection of primate and mouse cell lines with a recombinant vaccinia virus (vvgp41) expressing the truncated HIV-1 env gene. These results strongly suggest that (i) the two biological activities of the HIV-1 envelope glycoprotein can occur independently and (ii) the association of the two glycoprotein subunits may restrict the fusion activity of the transmembrane component to CD4+ cells.
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PMID:The transmembrane glycoprotein of human immunodeficiency virus type 1 induces syncytium formation in the absence of the receptor binding glycoprotein. 160 36

Five in-frame stop mutations in the HIV-1 env gene, which lead to the production of env gene products truncated within the cytoplasmic C-terminal tail, have been generated and their effects on membrane fusion capacity, glycoprotein incorporation into virus particles, infectivity, and cytopathogenicity were analyzed. The resulting truncated glycoproteins were processed normally, were transported to the cell surface, and were able to induce CD4-dependent membrane fusion. The membrane fusion capacity of one of the mutant glycoproteins with a truncation of 144 amino acids was increased to about double of that induced by wild-type glycoprotein. With a single exception, the truncated viral glycoproteins were incorporated into virus particles which were infectious and cytopathic for permissive MT-4 cells. The infection kinetics with the mutated viruses were, however, delayed to varying degrees in comparison to infection with wild-type virus. Nevertheless, in each case, PCR amplification and direct sequencing of viral DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA. The mutant virus encoding a viral glycoprotein with the longest truncation (144 amino acids), in which only 7 cytoplasmic C-terminal amino acids in gp41 remain, resulted in infection kinetics in MT-4 cells which were only marginally delayed in comparison to those induced by wild-type virus. This means that these C-terminal 144 amino acids of gp41 are not necessary for glycoprotein incorporation into virus particles nor do they significantly contribute to the infectivity nor the cytopathogenicity of HIV-1 in MT-4 cells.
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PMID:Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product. 160 8

Replication competent chimeric viruses that express the gag and pol proteins of SIVmac and the env proteins of HIV-1 were made. One such chimeric virus, SHIV-4, that expresses the vif, vpx, vpr, and nef regulatory genes of SIV and the tat and rev regulatory genes of HIV-1 replicated efficiently in cynomolgus monkeys. This model system can be used to evaluate the efficacy of anti-HIV-1 vaccines directed at the envelope glycoproteins, anti-HIV-1 envelope glycoprotein antiserum or monoclonal antibodies, and anti-HIV-1 drugs designed to inhibit the tat, rev, or env functions.
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PMID:Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. 161 62

A cell clone, L-2, which produces non-infectious doughnut-shaped human immunodeficiency virus type 1 (HIV-1) particles, was permissive for HIV-1 superinfection, which resulted in the production of infectious particles. The superinfection showed slow kinetics compared with primary HIV-1 infection of M10 cells, the parent of the L-2 cell clone. Inhibition studies on the superinfection of L-2 cells using several CD4-related reagents showed that the CD4 molecule was an essential component of the receptor for superinfection. Strong inhibitory effects were obtained using CD4 peptides such as CD4(68-130), which includes a portion homologous to the immunoglobulin third complementarity-determining region (CDR3), as well as recombinant soluble CD4. In contrast, a CD4(45-60) peptide, which includes most of the CDR2-related region, was not effective, although the Leu-3a monoclonal antibody (MAb), which recognizes a site near the CDR2-related region, did slightly, but significantly, delay the superinfection kinetics. Comparative flow cytometry of L-2 and M10 cells revealed that the cell surface of L-2 cells despite expressing HIV-1 env protein, reacted slightly with OKT4 or anti-CD4(68-130) MAb, but not with Leu-3a or OKT4A MAb. In contrast, no reaction was detected with any of these anti-CD4 MAbs on the surface of another HIV-1 superinfection-resistant cell clone, MOLT-#8IIIB-14, which expresses HIV-1 env proteins but does not produce infectious HIV-1 particles. These results strongly suggest that expression of the CD4 major receptor site for primary HIV-1 infection is preferentially decreased on the surface of L-2 cells, but that the OKT4 epitope and the nearby region corresponding to immunoglobulin CDR3 remain exposed on the cell surface. Consequently, the CD4 CDR3-related region could play a major role as the receptor for the superinfection reported here.
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PMID:Human immunodeficiency virus type 1 (HIV-1) superinfection of a cell clone converting it from production of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than the major binding site for HIV-1 glycoproteins. 162 1

The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev stimulates expression of structural viral proteins via a target response element (RRE) located within gag-pol and env mRNAs. To analyse the HIV-2 Rev trans-activation effect on the expression of the envelope protein, we cloned a functionally active HIV-2 rev cDNA and showed that it contained four exons. Using transient expression assays, we mapped a 353 bp RRE fragment within the env gene of HIV-2 on which both HIV-1 and HIV-2 Rev could act. Interestingly, smaller fragments suppressed the use of additional splice sites within the env gene and caused envelope protein expression independent of Rev.
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PMID:Functional mapping of the rev-responsive element of human immunodeficiency virus type 2 (HIV-2): influence of HIV-2 envelope-encoding sequences on HIV-1 gp120 expression in the presence or absence of Rev. 162 2

Our understanding of the biology and origins of human immunodeficiency virus type 2 (HIV-2) derives from studies of cultured isolates from urban populations experiencing epidemic infection and disease. To test the hypothesis that such isolates might represent only a subset of a larger, genetically more diverse group of viruses, we used nested polymerase chain reactions to characterize HIV-2 sequences in uncultured mononuclear blood cells of two healthy Liberian agricultural workers, from whom virus isolation was repeatedly unsuccessful, and from a culture-positive symptomatic urban dweller. Analysis of pol, env and long terminal repeat regions revealed the presence of three highly divergent HIV-2 strains, one of which (from one of the healthy subjects) was significantly more closely related to simian immunodeficiency viruses infecting sooty mangabeys and rhesus macaques (SIVSM/SIVMAC) than to any virus of human derivation. This subject also harboured multiply defective viral genotypes that resulted from hypermutation of G to A bases. Our results indicate that HIV-2, SIVSM and SIVMAC comprise a single, highly diverse group of lentiviruses which cannot be separated into distinct phylogenetic lineages according to species of origin.
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PMID:Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. 164 Oct 38

The requirement for tnv, a tat-env-rev fusion protein expressed by the IIIB strain of HIV-1, was tested. The expression of tnv was prevented by altering the 5' splice site that flanks the central coding exon of tnv. Mutants that carry such an altered 5' splice site replicate normally in an established T-cell line and in peripheral blood lymphocytes, demonstrating that tnv has no effect on virus replication. However, two mutants that carry an alteration in the 3' splice site of the same exon are replication defective. The 3' splice site mutations result in significant reduction in the expression of the 16-kDa tat protein and induce the expression of large amounts of a 19-kDa rev-related protein that initiates within the central coding exon of tnv. S1 nuclease analysis reveals that splicing to the central tnv exon occurs with substantially increased efficiency via the use of an alternate 3' splice site six nucleotides 3' from the mutated site. The effect of the 3' splice site mutations on viral protein expression and replication are fully reversed by a second site mutation that eliminates the alternate splice site.
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PMID:The role of the tnv protein and tnv RNA splicing signals in replication of HIV-1 IIIB isolates. 164 82

A simple, rapid, reproducible and sensitive peptide-Time-Resolved-Fluoroimmunoassay (TR-FIA) method is described which allows the detection of antibodies to the Human Immunodeficiency Virus type 1 (HIV-1). By using a panel of synthetic peptide antigens that covered env, gag and pol amino acid sequences, a 20 amino acid peptide (GIWGCSGKLICTTAVPWNAS) describing an immunodominant and conserved domain on the gp41 region of the BH10 clone was found to be the most reactive in this study. Optimal conditions for antigen concentration, serum dilution and incubation time were established. The peptide-TR-FIA is specific, as assessed by testing HIV-1 positive sera which included samples from AIDS, ARC patients and HIV-positive drug users. The test was used to detect HIV antibodies in 250 well characterized HIV-1 positive sera and 50 normal sera. Peptide-TR-FIA results indicate that the env peptide was highly reactive with HIV-positive sera showing a sensitivity of 100%. None of the 50 control sera showed positive reactivity against the synthetic peptide. Furthermore the peptide-TR-FIA allowed a fine titration of antibodies to defined epitopes of immunodominant HIV structural proteins that usually cannot be achieved by peptide-ELISA assays.
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PMID:Detection of antibodies to human immunodeficiency virus type I by using synthetic peptides and time-resolved fluoroimmunoassay (TR-FIA). 164 52

The order of appearance of human immunodeficiency virus type 1 (HIV-1) nucleic acids was examined in monocyte-derived macrophages following a high multiplicity infection with macrophage-tropic virus. Using the polymerase chain reaction, viral DNA was first detected 2 h after infection and continued to accumulate over the next 24 h. Transcripts representing tat, rev and nef splicing were detected by 24 h, and transcripts representing env splicing were detected by 48 h after infection. Coincident with the appearance of env transcripts, new synthesis of cellular and extracellular p24 antigen began, multinucleated giant cells formed and progeny infectious virus emerged. This analytical system provides a foundation for further studies on the effects of antiviral agents and cellular factors on the replication cycle of HIV-1 in non-transformed, primary monocyte-derived macrophages.
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PMID:Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages. 164 35

The interaction of the Rev protein from human immunodeficiency virus type 1 (HIV-1) with the nucleocytoplasmic mRNA-transport system was investigated. In gel-shift assay, the recombinant Rev protein used in this study selectively bound to the Rev-responsive element (RRE) region of HIV-1 env-specific RNA. Nitrocellulose-filter-binding studies and Northern/Western-blotting experiments revealed an association constant of approximately 1 x 10(10) M-1. The Rev protein also strongly bound to isolated nuclear envelopes from H9 cells, containing the poly(A)-binding site (= mRNA carrier) and the nucleoside triphosphatase (= NTPase), which are thought to be involved in nuclear export of poly(A)-rich mRNA. Binding of 125I-Rev to a 110-kDa nuclear-envelope protein, the putative mRNA carrier, could be demonstrated in in vitro experiments. Both efflux of cellular poly(A)-rich RNA, such as actin RNA [but not efflux of poly(A)-free RNA] from isolated nuclei and the nuclear-envelope NTPase activity were strongly inhibited by Rev protein. On the other hand, transport of viral env RNA, containing the Rev-responsive element, was increased in the presence of Rev. Studying the release of RNA from closed nuclear-envelope vesicles containing entrapped RNA, the action of Rev was found to occur at the level of translocation of RNA through the nuclear pore. Evidence is presented that Rev down-regulates the NTPase-driven transport of mRNA lacking the RRE, most likely via binding to the mRNA carrier within the envelope. In contrast to the efflux of RRE-free RNA, ATP-dependent efflux of RRE-containing RNA from resealed nuclear-envelope vesicles was found to be increased, if the RNA was entrapped in the vesicles together with Rev protein. In addition, it was found that phosphorylated Rev, which is transported together with RRE-containing RNA out of the vesicles, becomes dephosphorylated during transport. In the vesicle experiments it is demonstrated for the first time that a protein selectively channels a specific mRNA across the nuclear-envelope pore complex.
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PMID:Evidence for a direct interaction of Rev protein with nuclear envelop mRNA-translocation system. 164 87


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