Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inactivated, partially purified simian immunodeficiency virus (SIVmac) protected macaques from intravenous challenge with homologous and heterologous strains of SIV that had been grown on human cells but no protection against challenge with monkey peripheral blood mononuclear cell-grown SIVmac was afforded. Human immunodeficiency virus type 1 prepared in an analogous way to the SIVmac vaccine on the C8166 human T cell line protected macaques against challenge with human cell-grown SIVmac. These results suggest that protection may be mediated by xenoimmunization with the vaccine cell substrate proteins. All vaccinated macaques had anti-cell antibodies. Major reactivity to MHC class I antigens was found as well as to a 70-kD protein detectable only under nonreducing conditions.
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PMID:Studies on the specificity of the vaccine effect elicited by inactivated simian immunodeficiency virus. 842 14

Packaging of retroviral RNA is attained through the specific recognition of a cis-acting encapsidation site (located near the 5' end of the viral RNA) by components of the Gag precursor protein. Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) are two lentiviruses that lack apparent sequence similarity in their putative encapsidation regions. We used SIV vectors to determine whether HIV-1 particles can recognize the SIV encapsidation site and functionally propagate SIV nucleic acid. SIV nucleic acid was replicated by HIV-1 proteins. Thus, efficient lentivirus pseudotyping can take place at the RNA level. Direct examination of the RNA contents of virus particles indicated that encapsidation of this heterologous RNA is efficient. Characterization of deletion mutants in the untranslated leader region of SIV RNA indicates that only a very short region at the 5' end of the SIV RNA is needed for packaging. Comparison of this region with the corresponding region of HIV-1 reveals that both are marked by secondary structures that are likely to be similar. Thus, it is likely that a similar higher-order RNA structure is required for encapsidation.
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PMID:Simian immunodeficiency virus RNA is efficiently encapsidated by human immunodeficiency virus type 1 particles. 847 68

Human immunodeficiency virus type 2 (HIV-2) is more closely related to certain simian immunodeficiency viruses than to HIV-1. The HIV-1 and HIV-2 envelope (env) glycoproteins share only approximately 40% amino acid (aa) sequence homology. Additionally, HIV-1 and HIV-2 seem to differ in pathogenicity and in host range. In order to identify the functional domains of the HIV-2 env glycoprotein, e.g., the CD4 binding region, the membrane anchor, and the fusion site, and to compare them to equivalent sites of HIV-1, a set of recombinant vaccinia viruses (VV) was constructed expressing N-terminal overlapping env proteins of 863 (full-length gp160), 708, 534 (full-length gp120), 438, 332, 198, and 488 aa (internal deletion of aa 333-707). Upon infection, only env proteins comprising the amino-terminal half of the transmembrane protein were expressed on the cell surface. Such VV constructs also induced syncytia in CD4-positive cells. The syncytia were smaller when the cytoplasmic domain of the transmembrane protein was removed. The CD4 binding site of HIV-2 was located between the carboxy terminus of gp120 (aa 512) and aa 438. Thus the amino-terminal half of the transmembrane protein of HIV-2 is sufficient for cell surface localization of the env protein and syncytia induction. These properties are shared with the HIV-1 env protein and demonstrate a functional conservation among HIV-1 and HIV-2 despite their genetic and phenotypic heterogeneity.
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PMID:Mapping of the human immunodeficiency virus type 2 envelope glycoprotein CD4 binding region and fusion domain with truncated proteins expressed by recombinant vaccinia viruses. 848 Apr 26

Human immunodeficiency virus type 2 and the related simian immunodeficiency virus (SIV) contain a unique regulatory gene, vpx. The Vpx protein is packaged in mature virions and is required for efficient viral replication in peripheral blood lymphocytes and macrophages. To study the localization of Vpx in mature virions, conical and bar-shaped core structures of SIV from macaques (SIVmac) were purified. The SIVmac core has a density of approximately 1.25 g/cm3, compared with 1.16 g/cm3 for an intact virion. The relative proportions of major capsid protein (p27) and reverse transcriptase activity were similar for intact virions and core structures. The majority of matrix protein (p14) was removed from the purified core structure, suggesting its association with the viral membrane. Similarly, most of the Vpx protein was absent from the purified core structure. This result suggests that as with the matrix protein, the majority of Vpx proteins are localized outside the virus core. The localization of Vpx suggests that it may be involved in virus entry such as penetration or uncoating.
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PMID:Vpx of simian immunodeficiency virus is localized primarily outside the virus core in mature virions. 851 Feb 27

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. The simian immunodeficiency virus (SIV) causes a similar syndrome in macaques. The product of the nef gene of SIV has been shown to be important for virus replication and disease progression in vivo. In vitro, both SIV and HIV Nef downregulate surface expression of CD4 and accelerate total CD4 turnover. The mechanism by which Nef downregulates CD4 has not been established. A current model suggests that Nef enhances cell surface CD4 endocytosis and degradation in lysosomes. However, this was recently challenged when CD4 was found to accumulate in early endosomes of cells expressing Nef. Because inhibition of Nef function might halt virus replication and disease progression, we tested two macrolide antibiotics for their ability to inhibit Nef function. Concanamycin B (ConB) and bafilomycin A1 (BFLA1) are specific inhibitors of acidification of cell endosomes and lysosomes and, unlike other inhibitors, do not affect transport. Although ConB (25 nM) and BFLA1 (100 nM) blocked phorbol myristate acetate- and Nef-induced CD4 degradation in human monocyte U937 cells, CD4 surface expression was not recovered. Instead, CD4 accumulated in lysosomes. To determine if Nef is directly responsible for CD4 degradation or if they bind to each other in a manner similar to Vpu, transcripts of human CD4 and HIV-1 nef were cotranslated in vitro. Our results indicate that under our experimental conditions, Nef does not affect CD4 stability and does not associate with CD4 in this in vitro system. Our data suggest that (i) CD4 downregulation by Nef results in degradation of CD4 in lysosomes, (ii) inhibition of CD4 degradation by macrolide antibiotics does not restore surface expression, and (iii) the inhibition of CD4 expression by Nef appears to be indirect and is likely to involve cellular factors.
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PMID:Inhibition of Nef- and phorbol ester-induced CD4 degradation by macrolide antibiotics. 862 71

Human immunodeficiency virus type 1 (HIV-1) is restricted for replication in rhesus macaque cells and does not establish infection in this species. The block to productive infection of macaque peripheral blood mononuclear cells (PBMC) in culture was investigated. A chimeric virus SHIV containing HIV-1 tat, rev, and env and all other genes from a simian immunodeficiency virus clone pathogenic in macaques (i.e., SIVmec239) replicated efficiently in macaque PBMC. Thus, the attachment step, involving interaction of the HIV-1 env glycoprotein with the cell surface CD4 receptor, is not blocked. Analysis of uptake of HIV-1 particles in these cells revealed a small reduction in virion entry; however, viral DNA synthesis, measured by PCR amplification, was greatly reduced. Taken together, these results indicate that the block to HIV-1 (subtype B) replication in rhesus macaque cells involves release of the virion core into the cytoplasm and/or a step immediately prior to initiation of reverse transcription. Further studies are required to characterize this block through identification of species-specific cellular proteins that interact with HIV-1 proteins in the early phase of viral replication.
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PMID:Restriction of HIV-1 (subtype B) replication at the entry step in rhesus macaque cells. 863 16

Human immunodeficiency virus type 1 mutants that are resistant to inhibition by cyclosporins arise spontaneously in vitro during propagation in a HeLa-CD4+ cell line in the presence of a nonimmunosuppressive analog of cyclosporin A. Interestingly, the phenotype of all of the mutants examined is drug resistant and drug dependent, with both cyclosporin A and its analog. Four independently isolated mutants have been analyzed genetically by construction of recombinant proviruses in the NL4-3 parental strain background and subsequent testing of the chimeric viruses in HeLa cells. The cyclosporin-resistant, cyclosporin-dependent phenotype consistently transfers with a 1.3-kb fragment of gag, within which the four mutants share one of two possible single amino acid exchanges in a proline-rich stretch in the capsid domain of Pr55gag. These mutants provide the first evidence that mutations in human immunodeficiency virus type 1 gag confer resistance to cyclosporins; however, replication is conditional on the presence of the drug. In the T-cell line CEM, replication of the recombinant mutant viruses is also cyclosporin dependent. The drug-dependent replication in HeLa cells is stringent, and in the absence of cyclosporin only revertant viruses with the parental phenotype grow out of cultures infected with cyclosporin-dependent virus. In at least one isolate examined, the revertant phenotype appears to be due to suppressor mutations near the proline-rich region.
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PMID:Spontaneous mutations in the human immunodeficiency virus type 1 gag gene that affect viral replication in the presence of cyclosporins. 864 87

Lentiviruses are a subfamily of retroviruses that are characterized by long incubation periods between infection of the host and the manifestation of clinical disease. Human immunodeficiency virus type 1, the causative agent of AIDS, is the most widely studied lentivirus. However, the lentiviruses that infect sheep, goats, and horses were identified and studied prior to the emergence of human immunodeficiency virus type 1. These and other animal lentiviruses provide important systems in which to investigate the molecular pathogenesis of this family of viruses. This review will focus on two animal lentivirus models: the ovine lentivirus visna virus; and the simian lentivirus, simian immunodeficiency virus. These animal lentiviruses have been used to examine, in particular, the pathogenesis of lentivirus-induced central nervous system disease as models for humans with AIDS as well as other chronic diseases.
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PMID:Molecular biology and pathogenesis of animal lentivirus infections. 866 73

Human immunodeficiency virus type 1 (HIV-1) specifically incorporates the host cell peptidyl-prolyl isomerase cyclophilin A into virions via contacts with the capsid (CA) domain of the Gag polyprotein Pr55gag. The immunosuppressant drug cyclosporin A and the nonimmunosuppressive cyclosporin A analog SDZ NIM 811 bind to cyclophilin A and inhibit its incorporation into HIV-1 virions. Both drugs inhibit the virion association of cyclophilin A and the replication of HIV-1 with a similar dose dependence. In contrast, these compounds are inactive against other primate lentiviruses which do not incorporate cyclophilin A, such as simian immunodeficiency virus (SIV). To locate determinants which confer sensitivity to SDZ NIM 811, we generated chimeric proviruses between HIV-1 and SIVmac. A hybrid SIVmac which has the CA-p2 domain of the Gag polyprotein replaced by the corresponding domain from HIV-1 replicated in an established CD4+ cell line and in human but not macaque peripheral blood mononuclear cells. The transfer of the HIV-1 CA-p2 domain to SIVmac led to the efficient incorporation of cyclophilin A, and SDZ NIM 811 effectively inhibited both the virion association of cyclophilin A and the spread of the hybrid virus in infected cultures. We conclude that the HIV-1 CA-p2 domain contains determinants which confer the necessity to interact with cyclophilin A for efficient virus replication. Furthermore, our data show that the CA-p2 domain can play a crucial role in species tropism.
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PMID:The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811. 870 90

Human immunodeficiency virus type 2 infection is rare in children. This virus can be acquired through transfusion and also by the maternofetal route, especially when the mother becomes infected during pregnancy. Diagnosis based on specific serologic tests is simple after the age of 18 months. In the perinatal period, however, viral isolation by culture or polymerase chain reaction DNA amplification or both appears to be less sensitive than in the case of human immunodeficiency virus type 1. Disease progression is far slower than with human immunodeficiency virus type 1, but severe immunodeficiency can occur.
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PMID:Human immunodeficiency virus type 2 infection in children. 920 26


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