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

Antigenic epitopes on the major core (gag) protein of isolates of simian and human immunodeficiency virus (SIV and HIV) were compared using a panel of eleven mouse monoclonal antibodies (Mabs) that recognized nine distinct gag epitopes. Viral isolates used for comparison were HIV-1IIIb, HIV-2ROD, and SIV isolates from macaque (SIVmac), sooty mangabey (SIVsm-UCD), African green monkey (SIVagm), and stump-tailed macaque (SIVstm-UCD). The relatedness of the various HIV and SIV isolates, as determined by Mabs to core protein epitopes, paralleled that ascertained by genetic sequencing.
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PMID:Shared antigenic epitopes of the major core proteins of human and simian immunodeficiency virus isolates. 138 47

In a search for synthetic peptide antigens fit to detect anti-HIV antibodies, a set of algorithms were used to predict the probable antigenic determinants of gag, pol, env and nef proteins of HIV-1 and HIV-2. Over forty peptides were synthesized by the solid-phase method. The reactivity of the peptide antigens was evaluated in ELISA on panels of HIV-1/2-positive sera. Application of the synthetic peptides for the early HIV diagnostics was examined.
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PMID:[Study of the antigenic structure of human immunodeficiency virus using synthetic peptides]. 138 9

Beside the risk of infection via HIV-1-contaminated blood, ophthalmologists are especially interested in the possibility of HIV-1 infection via tears. Therefore we tried to isolate HIV-1 from tears of 50 HIV-1-infected persons in different stages of disease by reverse transcriptase (RT) and by p24-antigen (p24-AG) in the cultures. Simultaneously we tried to isolate HIV-1 in the supernatant from peripheral blood lymphocytes (PBL), which was successful in 32 of the 50 examined specimens. HIV-1 could not be isolated from the tears of these persons. In addition, polymerasechain-reaction (PCR) was performed to detect proviral sequences (gag, pol, env) of HIV-1 in tears and blood of ten HIV-1-infected patients. While in all the examined patients gag, pol and env could be detected in the blood samples, only one tear sample was found positive for gag and pol DNA fragments. These results indicate that tears of HIV-1-positive contain extremely low quantities of tissue culture infectious doses (TCID) of HIV-1 in contrast to PBL. HIV-1 infection via tears therefore appears to be unlikely.
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PMID:Infrequent detection of HIV-1 components in tears compared to blood of HIV-1-infected persons. 138 31

FL cells infected with vaccinia virus or its recombinant carrying the gag gene of human immunodeficiency virus type 1 (HIV-1) were examined by ultra-high-resolution scanning electron microscopy. Virions, whether located extracellularly or intracellularly, had a brick-shaped or watermelon appearance as a whole. Extracellular virions observed on the surface of infected cells had variable surface ultrastructures depending on the manner in which particular virions were wrapped in cell membranes. Most of the intracellular naked virions adherent to the inner face of cell surface membranes clearly exhibited ridgy, rod-shaped or globular surface structures on their surface. HIV-like particles with a diameter of about 100 nm and virions of vaccinia virus were both observed distinctly on the surface of FL cells infected with the recombinant virus.
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PMID:Ultra-high-resolution scanning electron microscopy of vaccinia virus and its recombinant carrying the gag gene of human immunodeficiency virus type 1. 140 23

Previous studies of the genetic and biologic characteristics of human immunodeficiency virus type 1 (HIV-1) have by necessity used tissue culture-derived virus. We recently reported the molecular cloning of four full-length HIV-1 genomes directly from uncultured human brain tissue (Y. Li, J. C. Kappes, J. A. Conway, R. W. Price, G. M. Shaw, and B. H. Hahn, J. Virol. 65:3973-3985, 1991). In this report, we describe the biologic properties of these four clones and the complete nucleotide sequences and genome organization of two of them. Clones HIV-1YU-2 and HIV-1YU-10 were 9,174 and 9,176 nucleotides in length, differed by 0.26% in nucleotide sequence, and except for a frameshift mutation in the pol gene in HIV-1YU-10, contained open reading frames corresponding to 5'-gag-pol-vif-vpr-tat-rev-vpu-env-nef-3' flanked by long terminal repeats. HIV-1YU-2 was fully replication competent, while HIV-1YU-10 and two other clones, HIV-1YU-21 and HIV-1YU-32, were defective. All three defective clones, however, when transfected into Cos-1 cells in any pairwise combination, yielded virions that were replication competent and transmissible by cell-free passage. The cellular host range of HIV-1YU-2 was strictly limited to primary T lymphocytes and monocyte-macrophages, a property conferred by its external envelope glycoprotein. Phylogenetic analyses of HIV-1YU-2 gene sequences revealed this virus to be a member of the North American/European HIV-1 subgroup, with specific similarity to other monocyte-tropic viruses in its V3 envelope amino acid sequence. These results indicate that HIV-1 infection of brain is characterized by the persistence of mixtures of fully competent, minimally defective, and more substantially altered viral forms and that complementation among them is readily attainable. In addition, the limited degree of genotypic heterogeneity observed among HIV-1YU and other brain-derived viruses and their preferential tropism for monocyte-macrophages suggest that viral replication within the central nervous system may differ from that within the peripheral lymphoid compartment in significant and clinically important ways. The availability of genetically and biologically well characterized HIV-1 clones from uncultured human tissue should facilitate future studies of virus-cell interactions relevant to viral pathogenesis and drug and vaccine development.
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PMID:Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. 140 5

Subsequent to the discovery that RNA can have site specific cleavage activity, there has been a great deal of interest in the design and testing of trans-acting catalytic RNAs as both surrogate genetic tools and as therapeutic agents. We have been developing catalytic RNAs or ribozymes with target specificity for HIV-1 RNA and have been exploring chemical synthesis as one method for their production. To this end, we have chemically synthesized and experimentally analyzed chimeric catalysts consisting of DNA in the non-enzymatic portions, and RNA in the enzymatic core of hammerhead type ribozymes. Substitutions of DNA for RNA in the various stems of a hammerhead ribozyme have been analyzed in vitro for kinetic efficiency. One of the chimeric ribozymes used in this study, which harbors 24 bases of DNA capable of base-pairing interactions with an HIV-1 gag target, but maintains RNA in the catalytic center and in stem-loop II, has a sixfold greater kcat value than the all RNA counterpart. This increased activity appears to be the direct result of enhanced product dissociation. Interestingly, a chimeric ribozyme in which stem-loop II (which divides the catalytic core) is comprised of DNA, exhibited a marked reduction in cleavage activity, suggesting that DNA in this region of the ribozyme can impart a negative effect on the catalytic function of the ribozyme. DNA-RNA chimeric ribozymes transfected by cationic liposomes into human T-lymphocytes are more stable than their all-RNA counterparts. Enhanced catalytic turnover and stability in the absence of a significant effect on Km make chimeric ribozymes favorable candidates for therapeutic agents.
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PMID:Chimeric DNA-RNA hammerhead ribozymes have enhanced in vitro catalytic efficiency and increased stability in vivo. 140 57

Analysis of the immunological properties of recombinant proteins of HIV-1 gene gag-pol secreted by yeast cells S. cerevisiae was carried out. The proteins under study interacted with antibodies from HIV-1-seropositive human subjects and with antibodies of rabbit immune serum to the native virus as effectively and specifically as natural HIV-1 proteins. The yeast gag-pol-protein complex was markedly immunogenic and induced in animals synthesis of antibodies of a certain specificity spectrum. A comparative immunochemical analysis of the properties of the recombinant proteins carried out by EIA and immune blot showed a certain degree of similarity between the yeast proteins and those of analogous construction produced in E. coli system.
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PMID:[The antigenic and immunogenic properties of a recombinant protein of the HIV-1 gag-pol gene secreted by Saccharomyces cerevisiae yeast cells]. 141 8

A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of "safer sex" techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of "silent" HIV-1 infection in a high-risk seronegative population. Among the 58 FP, three were found to be HIV-1-seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures.
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PMID:Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population. 142 11

We have characterized an inhibitory RNA element in the human immunodeficiency virus type 1 (HIV-1) gag coding sequence that prevents gag expression. The inhibition exerted by this element could be overcome by the presence of the Rev-responsive element in cis and of Rev protein in trans. To understand the mechanism of function, we inactivated the inhibitory element by mutagenesis while maintaining an intact gag coding region. A constitutive high level of Rev-independent gag expression was achieved only after the introduction of 28 point mutations over a large region of 270 nucleotides within the gag coding region. To our knowledge, this is the first demonstration of inactivation of a negative RNA element within a coding region without alteration of the expressed protein. Elimination of the inhibitory element in the p17gag region, named INS-1, offered the opportunity to detect a second inhibitory element in the gag-pol region. The presence of either INS element is sufficient to inhibit gag expression, demonstrating that multiple INS elements acting independently can inhibit HIV RNA expression. Expression of gag from Rous sarcoma virus, a retrovirus that does not require Rev-like regulatory proteins, revealed that the Rous sarcoma virus p19gag region does not contain inhibitory elements. These results demonstrate the presence of a strong inhibitory element acting at the level of mRNA and provide a general method for the removal of such elements from mRNA coding regions. The inhibitory element functions in the absence of any HIV-1 proteins, suggesting that cellular factors are responsible for this inhibition.
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PMID:Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. 143 10

A 41-kDa unprocessed human immunodeficiency virus 2 (HIV-2) gag precursor protein that has a deletion of a portion of the viral protease assembles as virus-like particles by budding through the cytoplasmic membrane of recombinant baculovirus-infected insect cells. We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the neutralizing and the CD4 binding domains (V3+CD4BD) of gp120 env gene sequences from HIV-1 or HIV-2. The env gene sequences were inserted either into the middle of the gag gene or at the 3' terminus of the gag gene. Virus-like particles were formed by chimeric gene products only when the env gene sequences were linked to the 3' terminus of the gag gene. Insertion of env gene sequence in the middle of the gag gene resulted in high-level chimeric gene expression but without the formation of virus-like particles. Three different chimeric genes [gag gene with HIV-1 V3 (1V3), gag gene with HIV-2 V3 (2V3), and gag gene with HIV-2 V3+CD4BD (2V3+CD4BD)] formed virus-like particles that were secreted into the cell culture medium. In contrast, the HIV-1 V3+CD4BD/HIV-2 gag construct did not form virus-like particles. The chimeric gag-env particles had spherical morphology and the size was slightly larger than that of the gag particles, but the chimeric particles were similar to the mature HIV particles. Western blot analysis showed that the gag-env chimeric proteins were recognized by antibodies in HIV-positive human serum and rabbit anti-gp120 serum. Rabbit anti-gag 1V3 and anti-gag 2V3 sera reacted with authentic gp120 of HIV-1 and HIV-2, respectively, and neutralized homologous HIV infectivity. Our results show that precursor gag protein has potential as a carrier for the presentation of foreign epitopes in good immunological context. The gag protein is highly immunogenic and has the ability to carry large foreign inserts; as such, it offers an attractive approach for HIV vaccine development.
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PMID:Chimeric gag-V3 virus-like particles of human immunodeficiency virus induce virus-neutralizing antibodies. 143 41


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