Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retroviral gag nucleocapsid protein NCp7 (72 amino acids) of HIV-1 (LAV strain), which contains two successive zinc fingers of the Cys-X2-Cys-X4-His-X4-Cys form linked by a stretch of basic residues, promotes viral RNA dimerization and encapsidation and activates annealing of the primer tRNA to the initiation site of reverse transcription. The structure of NCp7 and other shorter fragments was studied by 600 MHz 1H nuclear magnetic resonance (NMR) in aqueous solution to account for its various biological properties. Complete sequence specific 1H NMR assignments of the 13-51 residues of NCp7 encompassing the two zinc fingers was achieved by two-dimensional NMR experiments and the three-dimensional structure of (13-51)NCp7 was deduced from DIANA calculations, using nuclear Overhauser effects as constraints. The structure of the zinc complexed form of NCp7 is characterized by a kink at the Pro31 level in the basic Arg29-Ala-Pro-Arg-Lys-Lys-Gly35 RNA binding linker leading to a proximity of the Lys14-Cys18 to the Gly35-Cys39 sequences, which belong to the folded proximal and distal zinc fingers, respectively. Accordingly, the aromatic residues Phe16 and Trp37 were found to be spatially close. The Lys33 and Lys34 side-chains involved in viral RNA dimerization were solvent exposed. The N- and C-terminal sequences of NCp7 behave as flexible independent domains. The proposed structure of NCp7 might be used to rationally design new anti-viral agents aimed at inhibiting its functions.
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PMID:Determination of the structure of the nucleocapsid protein NCp7 from the human immunodeficiency virus type 1 by 1H NMR. 163 74

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

cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA.
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PMID:Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. 165 66

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
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PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

RNA pseudoknot structural motifs could have implications for a wide range of biological processes of RNAs. In this study, the potential RNA pseudoknots just downstream from the known and suspected retroviral frame-shift sites were predicted in the Rous sarcoma virus, primate immunodeficiency viruses (HIV-1, HIV-2, and SIV), equine infectious anemia virus, visna virus, bovine leukemia virus, human T-cell leukemia virus (types I and II), mouse mammary tumor virus, Mason-Pfizer monkey virus, and simian SRV-1 type-D retrovirus. Also, the putative RNA pseudoknots were detected in the gag-pol overlaps of two retrotransposons of Drosophila, 17.6 and gypsy, and the mouse intracisternal A particle. For each sequence, the thermodynamic stability and statistical significance of the secondary structure involved in the predicted tertiary structure were assessed and compared. Our results show that the stem-loop structures in the pseudoknots are both thermodynamically highly stable and statistically significant relative to other such configurations that potentially occur in the gag-pol or gag-pro and pro-pol junction domains of these viruses (300 nucleotides upstream and downstream from the possible frameshift sites are included). Moreover, the structural features of the predicted pseudoknots following the frameshift site of pro-pol overlaps of the HTLV-1 and HTLV-2 retroviruses are structurally well conserved. The occurrence of eight compensatory base changes in the tertiary interaction of the two related sequences allow the conservation of their tertiary structures in spite of the sequence divergence. The results support the possible control mechanism for frameshifting proposed by Brierley et al. and Jacks et al.
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PMID:RNA pseudoknots downstream of the frameshift sites of retroviruses. 166 82

The purpose of this study was to define further the determinants of substrate specificity of HIV-1 PR. Rather than using small peptides, we used an in vitro system which permitted us to evaluate the effect of a mutated site within the context of its natural precursor. We made single-amino-acid substitutions around two sites which are processed by the HIV-1 PR. The Tyr/Pro site within gag appears to encode highly specific determinants which direct proteinase processing between MA and CA. The Phe/Pro site in pol, however, appears to be far more tolerant to amino acid substitutions, as none of our single-amino-acid substitutions blocked cleavage at or around this site. The increased tolerance of the Phe/Pro site may indicate that at this site, structural features are more important determinants of cleavage than primary amino acid sequence. We have shown that sequences outside of those encoding mature PR can inhibit proteolytic processing in this system. By preventing PR from cleaving itself from the polyprotein prematurely, p6* sequences would regulate morphogenesis and infectious particle formation. Late in infection, when the protein concentration of gag and gag/pol polyproteins at the cell surface becomes very high, cooperative protein-protein interactions may cause alterations of a p6*-PR interaction, relieving repression and permitting autocatalysis.
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PMID:Mutational analysis of a native substrate of the HIV-1 proteinase. 166 51

HIV-1 and HIV-2 both cause AIDS in humans. Simian immunodeficiency viruses (SIV) are non-human primate lentiviruses and the closest known relatives of the HIVs. They closely parallel HIVs in genomic organization and biologic properties. The authors discuss the known HIVs and SIVs of African origin and describe the variability which exists in the different groups. HIV-1 and HIV-2 share approximately 55-60% amino-acid homology in gag and pol, the genes most highly conserved among related retroviruses. HIV-1 is spread widely throughout the world, while HIV-2 infection appears to be concentrated in West Africa. Rare cases of HIV-2 infection have, however, been identified in Europe and America, usually in individuals connected with West Africa. The authors discuss viral genetic variation and variation of biological phenotype, and findings on HIV-1 and HIV-2 from Zaire, Uganda, Cameroon, Tanzania, Ethiopia, Congo, Ghana, the Gambia, Guinea-Bissau, and Cote d'Ivoire.
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PMID:Variability among HIV and SIV strains of African origin. 166 22

A homosexual man with histologically confirmed Kaposi's sarcoma remained seronegative for HIV-1, HIV-2, and HTLV-1 on conventional tests over a 4-year period. HIV cultures were also negative on thirteen separate occasions. However, serum antibodies to synthetic peptide analogues of the gp41 and nef regions of HIV-1 were consistently detected on an enzyme immunoassay. Tests with the polymerase chain reaction with primers directed to the gag and env regions were negative. The antigens to which the antibodies were produced might have come from a defective HIV mutant, another retrovirus, or a hitherto unknown "agent of Kaposi's sarcoma" with similar antigenic epitopes.
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PMID:Antibodies to gp41 and nef in otherwise HIV-negative homosexual man with Kaposi's sarcoma. 167 98

Studies of lentivirus infection in ruminants, nonhuman primates, and humans suggest that virus infection of macrophages plays a central role in the disease process. To investigate whether human immunodeficiency virus type 1 (HIV-1) can infect chimpanzee macrophages, we recovered monocytes from peripheral blood mononuclear cells of HIV-1-negative animals and inoculated these and control human monocytes with a panel of four human-passaged monocytotropic virus strains and one chimpanzee-passaged isolate. HIV-1 infected human monocytes synthesized proviral DNA, viral mRNA, p24 antigen, and progeny virions. In contrast, except for the chimpanzee-passaged HIV-1 isolate, chimpanzee monocytes failed to support HIV-1 replication when cultured under both identical and a variety of other conditions. Proviral DNA was demonstrated only at background levels in these cell cultures by polymerase chain reaction for gag- and env-related sequences. Interestingly, the chimpanzee-passaged HIV-1 isolate did not replicate in human monocytes; viral p24 antigens and progeny virions were not detected. The same monocytotropic panel of HIV-1 strains replicated in both human and chimpanzee CD4+ T lymphoblasts treated with phytohemagglutinin and interleukin-2. The failure of HIV-1 to infect chimpanzee monocytes, which can be overcome by serial in vivo viral passage, occurs through a block early in the viral life cycle.
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PMID:The inability of human immunodeficiency virus to infect chimpanzee monocytes can be overcome by serial viral passage in vivo. 167 68

During 1989, 316 members of a cohort of homosexual men were tested for HIV-specific DNA by the polymerase chain reaction (PCR) using a pair of gag-region primers. Of 125 HIV-seronegative subjects, 123 (98.4%) were PCR-negative while 158 (82.7%) of 191 HIV-seropositive subjects were PCR-positive. Fewer of the 33 subjects who were seropositive and PCR-negative were at Centers for Disease Control (CDC) stage IV than the seropositive, PCR-positive subjects (6 versus 25%; P = 0.030). The seropositive, PCR-negative group had higher mean CD4 counts (640 versus 490 x 10(6) cells/l; P = 0.006), higher CD4: CD8 ratios (0.92 versus 0.64; P = 0.004), lower immunoglobulin (Ig) G levels (1290 versus 1645 mg/dl; P = 0.002), lower IgA levels (168 versus 251 mg/dl; P less than 0.001), and lower C1q binding activity (8 versus 14%; P = 0.010) than the seropositive, PCR-positive subjects. The median rate of CD4 cell decline in the 3 years preceding the PCR sample was less marked in the seropositive, PCR-negative group than the seropositive, PCR-positive group (-58 versus -77 x 10(6) cells/l per year; P = 0.028). To control for duration of infection, we restricted the analysis to the subgroups of 11 seropositive, PCR-negative subjects and 34 seropositive, PCR-positive subjects who had seroconverted earlier in the cohort study. Both subgroups had similar durations of infection, yet the same pattern of differences persisted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low HIV-1 proviral DNA burden detected by negative polymerase chain reaction in seropositive individuals correlates with slower disease progression. 167 80


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