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

Serosurveys conducted prior to 1988 indicated a very low level of HIV-1 infection in Thailand, even among high-risk groups. The Ministry of Health has reported a dramatic increase in HIV-1 infection during the last three years. The geographic and demographic distribution of the epidemic is broad, involving multiple provinces and risk groups. Foci of higher incidence and prevalence have been noted in the urban center of Bangkok and in the northern provinces of Chiang Mai and Chiang Rai. Here we report the results of genetic characterization of 16 HIV-1 isolates from Thailand using a combination of polymerase chain reaction (PCR) typing and DNA sequencing. The complete sequence of gp160 (env) of five isolates, partial env sequence of six additional isolates, and the gag gene of two isolates were determined. Two highly distinct HIV-1 variants were found. One variant resembled those prevalent in North America and Europe; five of the isolates were of this type. The remaining eleven isolates were very similar to one another and represented a variant unlike any previously described. Phylogenetic tree analysis of complete env and gag genes placed the two variants on widely separated branches. Protein sequence comparisons indicate both general and specific features that distinguish the Northern Thailand variant both from the Bangkok variant and from virtually all previously sequenced HIV-1 isolates. A simple PCR test for distinguishing the two variants has been developed for use in epidemiologic surveys.
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PMID:Genetic variants of HIV-1 in Thailand. 148 77

Recombinant human adenoviruses (Ads) (types 4, 5, and 7) expressing the HIV-1 envelope membrane glycoprotein (gp160) were tested for immunogenicity in the dog. Administration of recombinant Ad7-env by intratracheal inoculation resulted in a low serum antibody response to gp160, which developed over several weeks. A strong neutralizing antibody response to the Ad7 vector developed within 1 week of infection. A subsequent booster inoculation 12 weeks later with the heterotypic Ad4-env recombinant virus resulted in significantly enhanced humoral responses directed at the envelope antigen, as measured by both ELISA and Western blot analysis as well as high-titer type-specific neutralizing antibodies, with some animals achieving neutralization titers approaching 1000. Recombinant HIV envelope glycoprotein derived from Ad-HIV-infected cell cultures was used as a subunit booster injection for dogs that had previously received sequential immunizations with heterotypic recombinant Ads. Significant immune responses against the envelope developed as measured by ELISA, Western blot analysis, and neutralization assays. These data indicate that live recombinant Ad-HIV vaccines are capable of inducing high-titer type-specific neutralizing antibodies to gp160 in vivo. Recombinant HIV envelope glycoprotein subunit vaccines, prepared from Ad-env-infected cells, are capable of boosting these responses.
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PMID:Adenovirus-human immunodeficiency virus (HIV) envelope recombinant vaccines elicit high-titered HIV-neutralizing antibodies in the dog model. 150 97

A series of recent studies have reported detection by the polymerase chain reaction (PCR) of cell-free human immunodeficiency virus type 1 (HIV-1) DNA (as opposed to virion RNA) in serum from both seropositive and seronegative persons. To evaluate the sensitivity, specificity, and reproducibility of PCR detection of cell-free HIV-1 DNA, we distributed coded panels containing 98 serum specimens obtained from well-characterized, infected individuals and control blood donors to the two laboratories with reported experience with this technique. Positive results were reported with HIV-1 gag primers (SK38/39) for 48 of 188 separate PCR determinations on DNA extracts from 44 serum samples from seropositive patients (25.5% sensitivity). HIV-1 gag signal was also reported for 28 of 151 PCR determinations on 34 samples from noninfected blood donors (18.5% false-positive rate). PCR for HIV-1 env DNA performed in one laboratory was negative on all specimens from seropositive and seronegative patients. Results for cell-free HIV-1 gag and human genomic (beta-globin or HLA DQ-alpha) DNA were inconsistent on replicate and serial specimens evaluated within each laboratory and between laboratories. These results indicate that current techniques for detecting cell-free HIV-1 DNA in serum lack adequate sensitivity, specificity, and reproducibility for widespread clinical applications.
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PMID:Poor sensitivity, specificity, and reproducibility of detection of HIV-1 DNA in serum by polymerase chain reaction. The Transfusion Safety Study Group. 151 86

The nucleotide sequences of the env genes of eight phenotypically heterogeneous human immunodeficiency virus type 1 (HIV-1) clones recovered from a single individual within a 3-week period were compared. In addition, the accessory gene sequences for four of these clones were obtained. Variation among most accessory genes was limited. In contrast, pronounced phenotype-associated sequence variation was observed in the env gene. At least three of these clones most likely resulted from genetic recombination events in vivo, indicating that this phenomenon may account for the emergence of proviruses with novel phenotypic properties. Within the env genes of the eight clones, four domains could be defined, the sequence of each of which clustered in two groups with high internal homology but 11 to 30% cluster variation. The extensive env gene variation among these eight clones could largely be explained by the unique manner in which the alleles of these four domains were combined in each clone. Experiments with chimeric proviruses demonstrated that the HIV-1 env gene determined the capacity to induce syncytia and tropism for T-cell lines. Amino acids previously shown to be involved in gp120-CD4 and gp120-gp41 interaction were completely conserved among these eight clones. The finding of identical V3 sequences in clones differing in tropism for primary monocytes and T-cell lines demonstrated the existence of determinants of tropism outside the env V3 region.
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PMID:Phenotype-associated env gene variation among eight related human immunodeficiency virus type 1 clones: evidence for in vivo recombination and determinants of cytotropism outside the V3 domain. 152 55

To detect latent infection with human immunodeficiency virus (HIV), specimens of peripheral blood leukocytes from HIV-seronegative hemophiliacs and from sexual partners of HIV-seropositive hemophiliacs were examined by polymerase chain reaction (PCR). The primer pair SK 38/39 derived from the gag region and/or the primer pair SK 68/69 corresponding to a conserved region of the env gene were used. Whereas HIV proviral DNA was detected by PCR in samples from 86 (97%) of 89 HIV-seropositive hemophiliacs, no HIV-DNA was found in blood samples of 198 HIV-seronegative hemophiliacs at risk. Of 40 HIV-seronegative sexual partners of HIV-infected hemophiliacs, none was PCR positive. Thus, PCR is proving to be a sensitive method by which to confirm infection in seropositive hemophiliacs, while the negative results in HIV-seronegative hemophiliacs and HIV-seronegative sexual partners of HIV-seropositive hemophiliacs suggest that a prolonged seronegative period of latent HIV infection is the exception.
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PMID:Absence of human immunodeficiency virus (HIV) proviral sequences in seronegative hemophilic men and sexual partners of HIV-seropositive hemophiliacs. 154 15

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

Human immunodeficiency virus type I (HIV-1) encodes a regulatory protein, Rev, which is required for cytoplasmic expression of incompletely spliced viral mRNA. Rev activity is mediated through specific binding to a cis-acting Rev responsive element (RRE) located within the env region of HIV-1. A monomer Rev binding site corresponding to 37 nucleotides of the RRE (IIB RNA) was studied by RNA footprinting, modification interference experiments and mutational analysis. Surprisingly, a 17 amino acid peptide, corresponding to the basic domain of Rev, binds specifically to this site at essentially identical nucleotides and probably induces additional base pairing. The Rev protein and related peptide interact primarily with two sets of nucleotides located at the junction of single and double stranded regions, and at an additional site located within a helix. This suggests that the domains of proteins responsible for specific RNA binding can be remarkably small and that the interaction between RNA and protein can probably induce structure in both constituents.
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PMID:Specific binding of a basic peptide from HIV-1 Rev. 154 76

Endogenous retrovirus-related sequences exist within the normal genomic DNA of all eukaryotes, and these endogenous sequences have been shown to be important to the nature and biology of related exogenous retroviruses and may also play a role in cellular functions. To date, no endogenous sequences related to human immunodeficiency virus type 1 (HIV-1) have been reported. Herein we describe the first report of the presence of nucleotide sequences related to HIV-1 in human, chimpanzee, and rhesus monkey DNAs from normal uninfected individuals. We also present the isolation and characterization of two of these endogenous HIV-1-related sequences, EHS-1 and EHS-2. With use of low-stringency Southern blot hybridization, complex banding patterns were detected in human DNA with 5' and 3' HIV-1-derived probes. When an HIV-1 env region probe was used, we detected a less complex, conserved banding pattern in human DNA as well as a related but distinct banding pattern in chimpanzee and rhesus monkey DNAs. EHS-1 and -2 were cloned from normal human genomic DNA libraries by using the env region probe. Clone EHS-1 shows sequence similarity with the domain of the envelope cellular protease cleavage site of HIV-1, while EHS-2 has sequence similarity to the overlapping reading frame for Rev and gp41. Stringent hybridization of EHS-1 back to primate genomic DNA indicates two distinct EHS-1 loci in normal human DNA, an identical band pattern in chimpanzee DNA, and a single locus in rhesus monkey DNA. Likewise, EHS-2 is present as a single highly conserved locus in all three species. An oligonucleotide derived from EHS-2 across a region of near identity to HIV-1 detects a complex banding pattern in all primates tested similar to that seen with the 3' HIV-1 probe. These data suggest that most of the HIV-1-related sequences identified in primate DNA share a common core of nucleic acid sequence found in both EHS-2 and rev and that some of these HIV-1-related sequences have additional larger regions of sequence similarity to HIV-1.
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PMID:Novel human endogenous sequences related to human immunodeficiency virus type 1. 154 56

The human retroviruses human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) are characterized by complex regulation of gene expression. Each virus encodes a posttranscriptional regulator, the 19-kDa HIV-1 Rev protein and the 27-kDa HTLV-I Rex protein, which is required for viral replication. Expression of these trans activators results in the cytoplasmic accumulation of unspliced or singly spliced viral mRNA which encode the gag, pol, and env gene products. The finding that the HTLV-I Rex protein is able to functionally substitute for the Rev protein of HIV-1 indicates that HIV-1 Rev and HTLV-I Rex may interact with the same component of a cellular pathway involved in either mRNA splicing or transport. In this study, we have generated functional Rev/Rex hybrid proteins by domain exchange. We have defined, using in vivo and in vitro analyses, the activation domains of Rev and Rex which are the putative targets of a common host cell factor(s) required for Rev and Rex function.
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PMID:Definition of the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange. 154 84

Human immunodeficiency virus type 1 (HIV-1), the agent of AIDS, frequently infects the central nervous system. We inoculated adult human brain cultures with chimeric viruses containing parts of the env gene of a cloned primary isolate from brain tissue, HIV-1 JRFl, inserted into the cloned DNA of a T-cell-tropic strain. A chimeric virus containing the carboxy-terminal portion of HIV-1 JRFl env did not replicate in these brain tissue cultures, while a chimera expressing an env-encoded protein containing 158 amino acids of HIV-1 JRFl gp120, including the V3 loop, replicated well in brain microglial cells, as it does in blood macrophages. Infection of brain microglial cells with such a chimera was blocked by an antibody to the V3 loop of gp 120. Thus, env determinants in the region of gp120, outside the CD4-binding site and comprising the V3 loop, are critical for efficient viral binding to and/or entry into human brain microglia.
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PMID:Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. 154 85


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