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

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.
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PMID:Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate. 129 45

The envelope (Env) glycoproteins of human and simian immunodeficiency viruses (HIV and SIV) form noncovalently associated oligomers which mediate virus binding to the cell surface and fusion between the viral envelope and plasma membrane. A high-affinity interaction with CD4 is a critical step in this process. In this report, we show that Env protein dimers, but not monomers, can bind two CD4 molecules simultaneously. Multimeric CD4 binding may have important implications for Env protein-CD4 avidity, CD4-induced release of gp120, and subunit-subunit cooperativity during virus membrane fusion as well as for therapeutic strategies.
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PMID:Multimeric CD4 binding exhibited by human and simian immunodeficiency virus envelope protein dimers. 150 Dec 94

To understand the role of the HIV-1 envelope protein in the assembly of virus, we constructed a proviral clone of HIV-1 where the methionine initiator codon of the env gene was substituted with a translational stop codon. Upon DNA transfection into permissive cells in culture, this clone produces virus-like particles similar in size to parental virus but are noninfectious in human T-cells, promonocytic cells, and primary macrophages. This mutant readily recombines with a deletion mutant provirus lacking the entire gag-pol region producing a recombinant virus that is infectious. Substitution of the same initiator methionine codon with valine results in a leaky missense mutant provirus capable of a low level of Env protein synthesis that leads to a productive infection. Thus, the prototype initiation codon AUG is dispensable for virus infectivity. Further, the expression of the envelope protein is not a prerequisite for the assembly of the virus particles in the HIV-1 system. These noninfectious envelope-less particles revert readily to wild-type phenotype upon cotransfection with Env-producing plasmid DNAs.
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PMID:Biological characterization of noninfectious HIV-1 particles lacking the envelope protein. 154 56

The generation of biologically active proviral DNA clones of simian immunodeficiency virus (SIV) that give rise to infectious virions has allowed the detailed examination of genetic variation in experimentally inoculated monkeys. Studies of nucleotide sequences derived directly from circulating leukocytes of infected monkeys show that the SIV genome undergoes rapid and dramatic variation during the course of infection. The env gene is a major site for variation, and within the Env protein, hypervariable regions analogous to those previously defined for the human immunodeficiency virus type 1 (HIV-1) env gene are apparent. A major exception is the region corresponding to the V3 domain in HIV-1, which has been highly conserved in all SIV studies to date. These data notwithstanding, the role of SIV genetic variation in the pathogenesis of AIDS in monkeys remains unclear. Genetic variation within the env gene does not appear to be sufficient for the development of AIDS since significant variation is observed in both pathogenic and nonpathogenic SIV infections. Furthermore, although it generally is believed that env gene variation might allow HIV and SIV to avoid recognition and elimination by host immune responses, this premise has not been rigorously proven. The use of molecularly cloned SIV in monkey models has provided important quantitative and qualitative information on in vivo sequence variation, and these data, in turn, have laid the groundwork for addressing the undoubtedly complex functional significance of this variation.
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PMID:Genetic variation of simian immunodeficiency viruses in nonhuman primates. 157 Nov 96

We have used a panel of cDNA clones expressing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) mRNAs to study translation of these mRNAs in eucaryotic cells. The tat open reading frame (ORF) has a strong signal for translation initiation, while rev and vpu ORFs have weaker signals. The expression of downstream ORFs is inhibited in mRNAs that contain the tat ORF as the first ORF. In contrast, downstream ORFs are expressed efficiently from mRNAs that have rev or vpu as the first ORF. All env mRNAs contain the upstream vpu ORF. Expression of HIV-1 Env protein requires a weak vpu AUG, which allows leaky scanning to occur, thereby allowing ribosomes access to the downstream env ORF. We concluded that HIV-1 mRNAs are translated by the scanning mechanism and that expression of more than one protein from each mRNA was caused by leaky scanning at the first AUG of the mRNA.
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PMID:Mechanism of translation of monocistronic and multicistronic human immunodeficiency virus type 1 mRNAs. 172 99

The effect of Rev on cytoplasmic accumulation of the singly spliced human immunodeficiency virus type 1 (HIV-1) vif, vpr, and env/vpu RNAs was examined by using a quantitative RNA polymerase chain reaction (PCR) analysis following transfection of complete proviral molecular clones into lymphoid cells. Previously published studies using subgenomic env constructs in nonlymphoid cell types concluded that Rev was necessary for cytoplasmic accumulation of high levels of unspliced env RNA and that, by analogy, Rev must be necessary for the cytoplasmic accumulation of all HIV-1 RNAs that contain the Rev-responsive element (RRE). We confirm those results in COS cells. Unexpectedly, in lymphoid cells, we find that although Rev acts somewhat to increase the cytoplasmic level of full-length HIV-1 RNA, Rev has little or no effect on cytoplasmic accumulation of singly spliced HIV-1 RNAs. However, Env protein expression was greatly reduced in the absence of Rev. Analysis of the cytoplasmic RNA revealed that in the absence of Rev or the RRE, the cytoplasmic vif, vpr, and env/vpu 2 RNAs were not associated with polysomes but with a complex of 40S-80S in size. Consequently, efficient expression of the Vif, Vpr, Vpu, and Env proteins from these RNAs is dependent on Rev. These results exclude a mechanism whereby the sole function of Rev is simply to export RNAs from nucleus to cytoplasm. We discuss other models to take into account the dependence on Rev for efficient translation of cytoplasmic HIV-1 RNAs.
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PMID:Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. 182 22

We have examined genetic variation of the simian immunodeficiency virus (SIV) in four macaques inoculated with virions derived from molecular clones of proviral DNA. Our data demonstrated that the SIV genome is capable of rapid and extensive genetic variation. This variation was especially large in the env gene, where nucleotide substitution frequencies were as high as 10(-1)/site/year. In some env clones, a high G to A transition rate was observed that accounted for up to 79% of the observed nucleotide substitutions. Moreover, in env clones with a high G to A transition rate, multiple in-frame stop codons were generated exclusively at tryptophan codons. Another interesting observation was the lack of variation in the region analogous to the V3 loop in the HIV-1 Env protein. Considered together, these data have important implications for studies of pathogenesis and vaccine development in the SIV model system.
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PMID:The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques. 192 74

The Vif protein of human immunodeficiency virus type 1 (HIV-1) regulates viral infectivity. Virions produced in cell culture after transfection by a Vif-negative molecular clone show a dramatic decrease in infectivity for susceptible CD4+ cell lines, although the Vif protein does not appear to be a constituent of the viral particle. The exact mechanism by which Vif affects HIV-1 infectivity is so far unknown. We report the existence of structural homologies between Vif and a family of cysteine proteases and present evidence which suggests that one of the targets of Vif is the Env protein and more precisely the cytoplasmic domain of gp41. Vif was found to modify both the processing and conformation of the Env protein. Ethyl(25, 35)- 3[(5)-3-methyl-1-(3-methylbutylcarbamoyl)]oxirane-2-carboxylate, a specific inhibitor of cysteine proteases, inhibits the effect of Vif, as does the mutation of Cys-114 to Leu in Vif. Furthermore, Cys-114 of Vif produced in Escherichia coli, interacts directly with trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane. These observations suggest that a cysteine protease activity is associated with Vif and that this activity plays a role in Env maturation.
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PMID:A specific inhibitor of cysteine proteases impairs a Vif-dependent modification of human immunodeficiency virus type 1 Env protein. 199 46

The binding of human immunodeficiency virus type 1 (HIV-1) gp120env to CD4 is the first event leading to infection and represents an important target for possible therapeutic intervention. To provide a tool for screening and quantitation of the effects of drugs inhibiting the Env-CD4 interaction, we developed a simple, fast and quantitative bioassay measuring the fusion between two cell lines generated by stable transfection: one expressing high levels of HIV-1 proteins but no infectious virus (HL2/3), and the other expressing the CD4 receptor and containing an inducible chloramphenicol acetyltransferase (CAT) gene linked to the HIV-1 long terminal repeat (HLCD4-CAT). Upon cocultivation of HL2/3 and HLCD4-CAT cells, efficient cell fusion is observed within 8 h. The efficiency of fusion can be evaluated visually and quantitated by measuring CAT enzyme. This novel bioassay allows testing for drugs capable of interfering with the CD4-Env interaction. HL2/3 cell line secretes gp120env in the medium and can be used for the production of Env protein.
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PMID:A bioassay for HIV-1 based on Env-CD4 interaction. 207 9

It is now well documented that human immunodeficiency virus type 1 (HIV-1) induces encephalopathy in patients with AIDS. In vitro studies have implicated the envelope protein (gp120) as a factor which causes neuronal death. To better evaluate the role and elucidate the mechanisms of gp120 neurotoxicity, we have developed transgenic mice carrying a segment of the HIV-1 genome that expresses the viral gp160 protein under the control of the human neurofilament light gene promoter. In two separate lines of transgenic mice, the Env protein was found to be expressed in several nuclei of the brain stem and in the anterior horns of the spinal cord. The two lines showed identical patterns of Env expression. Neuropathological evaluation revealed numerous abnormal dendritic swellings in the immunostained motor neuron structures. Large and numerous neuritic swellings were also prominent in the nucleus gracilis and in the gracilis and cuneate fascicles. In addition, reactive astrocytosis was observed in several immunoreactive areas of the central nervous system. These transgenic mice offer a unique model to further investigate the role of HIV-1 Env protein in neuronal toxicity and to help elucidate the mechanisms that are involved.
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PMID:Neuronal expression of human immunodeficiency virus type 1 env proteins in transgenic mice: distribution in the central nervous system and pathological alterations. 747 88


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