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)

Two newly synthesized carbocyclic oxetanocin analogs, (+/-)-9-[(1 beta,2 alpha,3 beta)-2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine (cyclobut-A) and (+/-)-9-[(1 beta,2 alpha,3 beta)-2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine (cyclobut-G) were tested for activity against the infectivity of human immunodeficiency virus (HIV) in vitro. A number of other carbocyclic oxetanocin analogs failed to exert good antiretroviral effects. Both cyclobut-A and cyclobut-G protected CD4+ ATH8 cells against the infectivity and cytopathic effect of HIV type 1 (HIV-1) and suppressed proviral DNA synthesis in ATH8 cells exposed to HIV-1 in vitro at concentrations of 50 to 100 microM. These compounds also inhibited the in vitro infectivity of another human pathogenic retrovirus, HIV-2. Furthermore, both compounds completely suppressed the replication of a monocytotropic strain of HIV-1 in monocytes and macrophages at concentrations as low as 0.5 microM, as assessed by inhibition of HIV-1 p24 gag protein production. We also found that 2'-deoxyguanosine readily reversed the antiretroviral activity of cyclobut-G in our system, whereas the activity of cyclobut-A was hardly reversed by 2'-deoxyadenosine or 2'-deoxycytidine. We noted, however, that these compounds inhibited the proliferation of peripheral blood mononuclear cells at concentrations of greater than or equal to 100 microM in vitro. Although both cyclobut-A and cyclobut-G appear to have a certain level of in vitro toxicity, our observations may have theoretical and clinical implications in understanding the structure-activity relationships of antiretroviral agents active against HIV.
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PMID:Cyclobut-A and cyclobut-G, carbocyclic oxetanocin analogs that inhibit the replication of human immunodeficiency virus in T cells and monocytes and macrophages in vitro. 232 78

A category of viruses has been identified which is related to human immunodeficiency virus (HIV) but is more closely related to a group of simian retroviruses (STLV-III). These viruses named HTLV-IV, LAV-II, or SBL-6669, are prevalent in West-Africa. In this study, we analysed the cross-reactivity at the protein level between HTLV-IV and HIV (HTLV-IIIB). The results indicate that most people infected with HTLV-IV have antibodies that react to the major gag protein of HIV p 24. There is also a high degree of immunologic cross-reactivity between the pol gene products of HIV and HTLV-IV. Among these the endonuclease/integrase is more conserved than the reverse transcriptase. In contrast, the envelope glycoproteins that are the most frequently detected antigens by antibodies from exposed individuals are serotype specific. These data make the env gene products the most interesting antigens for serotype specific diagnosis of human retroviruses infections.
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PMID:A STLV-III related human retrovirus, HTLV-IV: analysis of cross-reactivity with the human immunodeficiency virus (HIV). 244 14

The nucleotide sequence of the human spumaretrovirus (HSRV) genome was determined. The 5' long terminal repeat region was analyzed by strong stop cDNA synthesis and S1 nuclease mapping. The length of the RU5 region was determined and found to be 346 nucleotides long. The 5' long terminal repeat is 1,123 base pairs long and is bound by an 18-base-pair primer-binding site complementary to the 3' end of mammalian lysine-1,2-specific tRNA. Open reading frames for gag and pol genes were identified. Surprisingly, the HSRV gag protein does not contain the cysteine motif of the nucleic acid-binding proteins found in and typical of all other retroviral gag proteins; instead the HSRV gag gene encodes a strongly basic protein reminiscent of those of hepatitis B virus and retrotransposons. The carboxy-terminal part of the HSRV gag gene products encodes a protease domain. The pol gene overlaps the gag gene and is postulated to be synthesized as a gag/pol precursor via translational frameshifting analogous to that of Rous sarcoma virus, with 7 nucleotides immediately upstream of the termination codons of gag conserved between the two viral genomes. The HSRV pol gene is 2,730 nucleotides long, and its deduced protein sequence is readily subdivided into three well-conserved domains, the reverse transcriptase, the RNase H, and the integrase. Although the degree of homology of the HSRV reverse transcriptase domain is highest to that of murine leukemia virus, the HSRV genomic organization is more similar to that of human and simian immunodeficiency viruses. The data justify classifying the spumaretroviruses as a third subfamily of Retroviridae.
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PMID:Analysis of the primary structure of the long terminal repeat and the gag and pol genes of the human spumaretrovirus. 245 55

The sequences of a set of 63 peptides of demonstrated T immunogenicity have been analyzed and compared with two different randomly generated sets of sequences. This study indicates a statistically significant tendency of T immunogenic peptides to be constituted of clusters of rare tetrapeptides, as evaluated from the available sequence data banks. This result has been used to locate potential T epitopes in the human immunodeficiency virus (HIV) gag protein. Four peptides corresponding to the best candidate T epitopes (chosen in regions of conserved sequence among different virus isolates) have been synthesized and found to be recognized by a HIV-1-specific, HLA-A2-restricted human cytotoxic T cell line.
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PMID:T-immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein. 246 6

Current candidate vaccines fail to protect primates against challenge with human immunodeficiency virus (HIV) in the presence of antibody responses; this underlines the importance of studying cell-mediated immunity to HIV and identifying specific epitopes that stimulate cytotoxic T lymphocytes (CTL). Using a recombinant vaccinia virus to express the gag protein of HIV-1 we found HLA class-I-restricted gag-specific CTL in thirteen out of fifteen healthy HIV seropositive patients. We then used short synthetic peptides in the lysis assay to screen for gag CTL epitopes. In one patient we have identified a peptide in p24 that is recognized by CTL in association with HLA-B27. This peptide, and further peptide sequences defined by these methods, could be incorporated in vaccines designed to induce cell-mediated immunity against HIV.
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PMID:HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. 246 19

Two cases of wild-born chimpanzees which were positive for HIV-1 antibodies were observed in Gabon. These animals were never experimentally exposed to HIV-1 and had no history of inoculation with human blood products. A retrovirus was isolated from one of these chimpanzees. Several of the viral proteins from this virus, designated SIVcpz-GAB-1 (simian immunodeficiency virus from chimpanzee), differed in molecular weight from the known corresponding HIV/SIV proteins. The major gag protein of SIVcpz migrated on SDS-PAGE with a relative molecular mass of 25.5 and the outer membrane proteins were 110, 155 and 185 kD, respectively. SIVcpz did not induce severe cytopathic effects in human and chimpanzee lymphocytes. Antigenically, SIVcpz seems to be closer to HIV-1 than to HIV-2 and the other SIVs. Nucleic acid hybridization experiments appear to indicate that the virus is different from HIV-1 and HIV-2.
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PMID:Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. 251 55

Antibodies to specific human immunodeficiency virus (HIV) polypeptides are important laboratory markers of HIV infection. We have used an antibody to the major structural gag protein p24 of HIV-1 virus to immunochemically localize this capsid antigen in lymphoid cells from seven of eight patients at risk for HIV infection and who presented with parotid lymphadenopathy and lymphoepithelial cysts of the parotid gland. A clinicopathological assessment of these two manifestations as they relate to HIV infection is also presented.
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PMID:Immunocytochemical identification of HIV (p24) antigen in parotid lymphoid lesions. 251 36

Simian immunodeficiency virus (SIV) is a lentivirus with genetic relatedness to the human immunodeficiency viruses (HIV-1 and HIV-2). It induces a fatal syndrome in rhesus monkeys that closely parallels the clinical course of AIDS in humans. The authors used double-labeling immunohistochemical procedures on rhesus lymph node and spleen taken during different time periods after SIV infection to localize the p27 gag protein to specific cellular immunophenotypes. In animals with follicular hyperplasia, viral protein was found associated predominantly with follicular dendritic cells. Many of these cells showed ultrastructural alterations consisting of swollen dendritic processes containing electron-dense material. Lentiviral particles were found associated with this cell type only rarely. In lymphoid tissues with other histopathologic changes, macrophages and multinucleate giant cells were the predominant cell types containing detectable quantities of viral protein; smaller numbers of p27+ lymphocytes were present. Ultrastructurally, viral particles were found within the extracellular space adjacent to tissue macrophages and within membrane-bound vacuoles of giant cells and tissue macrophages. These results show that certain histologic patterns seen during the course of infection correlate with the localization of viral antigen to specific cellular immunophenotypes and that during the disease course, viral protein is preferentially localized in sections of lymph node and spleen to cells of the macrophage and dendritic cell lineages.
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PMID:Cellular localization of simian immunodeficiency virus in lymphoid tissues. I. Immunohistochemistry and electron microscopy. 253 16

We have documented rare infection of baboons in their native habitat with simian immunodeficiency virus (SIV). Of 124 sera collected from yellow baboons in central Tanzania, two gave high readings by SIVagm ELISA (greater than 1.0) and moderate by SIVmac ELISA (0.5-1.0). These two sera gave strong reactions to the major SIVagm proteins, including gp130, by western blot analysis; their reactivity to SIVmac protein was considerably weaker. Similar testing of 155 sera from olive baboons of Ethiopia revealed no clearly positive sera. Thus, 2 of 279 baboon sera or 0.7% were positive for antibodies to SIV. The strong reactivity of the two positive yellow baboon sera with SIVagm proteins raises questions about whether these animals may have been infected by green monkeys in their native habitat; baboons occasionally prey upon and eat green monkeys. In addition to these two clearly positive samples, one olive baboon serum and one yellow baboon serum reacted only with major gag protein (p24-p26). Continued study of prevalence and diversity of SIV in primates will be important for understanding the history and evolution of primate lentiviruses and, it is hoped, the origins of viruses that cause AIDS in humans.
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PMID:Prevalence of antibodies to SIV in baboons in their native habitat. 254 34

The gag proteins of human retroviruses such as human immunodeficiency virus (HIV-1) are specifically myristoylated in their amino termini (1, 2, 3). N-myristoyl glycinal diethylacetal (N-Myr-GOA) and other N-Myr-compounds (N-Myr-Gly-GOA, N-Myr-Gly-Gly-GOA and N-Myr-Gly-Gly-Gly-GOA) were newly synthesized and investigated for activity of antimyristoylation of these gag proteins and for influence on viral replication. Of the N-Myr-compounds tested, N-Myr-GOA most severely inhibited the protein myristoylation; N-Myr-Gly-GOA also inhibited it, but moderately. Furthermore, it was observed that N-Myr-GOA at 20 microM caused noticeable inhibition (about 80%) of the production of mature HIV in the HIV-1-infected MT-4 cells. In this system, N-Myr-GOA substantially inhibited more than 90% of the N-myristoylation of p17 gag protein produced in the HIV-1-infected MT-4 cells. These results suggest that the N-myristoylation of p17 gag protein of HIV-1 may be essential in its structural assembly or maturation.
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PMID:Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells with N-myristoyl glycinal diethylacetal resulted in inhibition of virus production. 269 61


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