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

Synthetic peptides containing amino acid sequence 218-238 of the core protein p24 of human immunodeficiency virus type 1 (HIV-1) and progressively shorter sequences at its C-terminus, were tested for their effect on antigen dependent in vitro responses of peripheral blood lymphocytes (PBL) from normal human donors. A peptide as short as 7 amino acids, corresponding to a highly conserved sequence, was able to inhibit in a dose-dependent manner the induction of a specific primary antibody response to the sheep red cell (SRC) antigen, as well as the proliferative response to recall microbial antigens. The results of this study constitute additional evidence of the immunoinhibitory effects of HIV components and may help to unravel some of the pathogenic mechanisms of AIDS. Moreover, they are of potential relevance for the development of immunoprophylactic and therapeutic strategies.
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PMID:The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope. 138 21

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

To determine the factors governing inactivation and neutralization, physical, chemical, and biological assays were performed on a molecular clone of human immunodeficiency type 1 (HIV-1HXB3). This included quantitative electron microscopy, gp120 and p24 enzyme-linked immunosorbent assays, reverse, transcriptase assays, and quantitative infectivity assays. For freshly harvested stocks, the ratio of infectious to noninfectious viral particles ranged from 10(-4) to 10(-7) in viral stocks containing 10(9) to 10(10) physical particles per milliliter. There were relatively few gp120 knobs per HIV particle, mean approximately 10 when averaged over the total particle count. Each HIV particle contained a mean approximately 5 x 10(-17) g of p24 and approximately 2 x 10(-16) g of RNA polymerase, corresponding to about 1200 and 80 molecules, respectively. The spontaneous shedding of gp120 envelope proteins from virions was exponential, with a half-life approximately 30 hr. The loss of RNA polymerase activity in virons was also exponential, with a half-life approximately 40 hr. The physical breakup of virions and the dissolution of p24 core proteins were slow (half-life greater than 100 hr) compared to the gp120 shedding and polymerase loss rates. The decay of HIV-1 infectivity was found to obey superimposed single- and multihit kinetics. At short preincubation times, the loss of infectivity correlated with spontaneous shedding of gp120 from virions. At longer times, an accelerating decay rate indicated that HIV requires a minimal number of gp120 molecules for efficient infection of CD4+ cells. The blocking activity of recombinant soluble CD4 (sCD4) and phosphonoformate (foscarnet) varied with the number of gp120 molecules and number of active RNA polymerase molecules per virion, respectively. These results demonstrate that the physical state of virions greatly influences infectivity and neutralization. The knowledge gained from these findings will improve the reliability of in vitro assays, enhance the study of wild-type strains, and facilitate the evaluation of potential HIV therapeutics and vaccines.
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PMID:Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. 138 85

Recombinant plasmids containing reiterated human immunodeficiency virus type 1 (HIV-1) Rev response element (RRE) sequences were constructed to suppress Rev-dependent HIV-1 Gag expression. The mammalian expression vectors pMAMneo containing one, three, or six repeats of the RRE sequence were cotransfected with a HIV-1 HTLV-IIIB proviral DNA into HeLa cells. All three RRE expression plasmids reduced replication of HIV-1 with similar efficacy. Furthermore, the chimeric expression vector pCMV neoRRE6 x ----(containing six copies of the RRE sequence) was used to establish HeLa cell lines constitutively expressing RRE. A plasmid encoding a Rev-dependent HIV-1 p24 Gag protein was cotransfected with the wild-type Rev expression plasmid into three different RRE-expressing HeLa cell lines. p24 Gag protein production in the culture supernatants of the HeLaneoRRE cells was compared with two neo-expressing cell lines. Although all cell lines (HeLaneoRRE, HeLaneo) displayed similar transfection efficiencies, p24 Gag protein synthesis was markedly reduced in the RRE-expressing cell lines in comparison to the control cells.
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PMID:Expression of chimeric neo-Rev response element sequences interferes with Rev-dependent HIV-1 Gag expression. 139 Oct 35

Our objective was to map serial patterns of Western blot reactivity over time of a cohort of initially ELISA-negative, Western blot-indeterminate individuals from a high-risk group and to determine if these individuals were at increased risk of harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA, two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot indeterminate homosexual volunteers and 20 matched seronegative controls. Results showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most commonly observed Western blot patterns, occurring in 70% of individuals. Specific Western blot reactivity was dependent upon the particular immunoblot preparation being used and varied considerably on a longitudinal basis. No individual pattern appeared predictive of an increased likelihood of subsequent seroconversion to HIV-1 relative to controls. By all other criteria including polymerase chain reaction analysis, samples from 17 of 19 individuals remained negative for HIV-1 at each time point. Two individuals evolved from an indeterminate to a positive Western blot and, simultaneously, from a negative to a positive polymerase chain reaction analysis, during follow-up. Our conclusions were as follows. ELISA-negative, Western blot-indeterminate individuals from a high-risk group show marked variability in immunoblot findings over time, and these patterns do not appear predictive of an increased likelihood of infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indeterminate western blot patterns in a cohort of individuals at high risk for human immunodeficiency virus (HIV-1) exposure. 140 Aug 98

Statistical analysis of a limiting dilution assay (LDA) showed that the occurrence of infectious human immunodeficiency virus type 1 (HIV-1)-harboring cells in serially diluted samples of peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive patients fits the model describing a single-hit Poisson distribution. This observation led to the discovery that there is a direct correlation (r = 0.957) between the number of HIV-1-positive cells and the time when viral culture produces 1 ng of the HIV-1 p24 gag protein per ml. Frequency estimates based on this relationship were highly accurate (P less than 0.01) within the first 15 days of viral culture, which consisted of coculture of 10(6) normal PBMCs with the equivalent number of test PBMCs. This approach was less cumbersome than LDA and was sensitive enough to detect a single infectious HIV-1-harboring cell among as many as 320,000 cells. The values obtained for 57 patients agreed well with the data in the literature and showed that the frequencies of infectious cells in PBMCs reflect the advancement in the clinical stage, being 1/38,000, 1/11,000, and 1/7,000 for asymptomatic patients (Centers for Disease Control [CDC] group II/III), patients with AIDS-related complex (CDC group IVa), and patients with AIDS (CDC group IVb/c), respectively. A nearly 10-fold disparity in mean frequencies was observed when these values were correlated with the numbers of CD4-positive cells (1/9,000, 1/1,500, and 1/300, respectively, for asymptomatic patients, patients with AIDS-related complex, and patients with AIDS). The described method provides a simple means of determining infectious HIV-1-positive cells in blood samples.
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PMID:Relationship between frequency of infectious human immunodeficiency virus type 1-harboring cells and kinetics of viral replication: a simple procedure for quantitation of infectious virus-carrying cells in blood samples. 140 Sep 50

The p24 antigen is only detectable in a minority of asymptomatic HIV infected individuals, which is in part felt to be secondary to immune complex formation with p24 antibody. We sought to determine if the recovery of p24 antigen could be enhanced by an acidification procedure in an attempt to dissociate p24 antibody-antigen complexes. We tested 291 HIV antibody positive serum samples in duplicate, comparing the standard Coulter p24 Antigen Assay with the same assay which was modified by pretreating samples for 60 min with 1.5 M glycine (pH 1.85) and then neutralizing the sample with 1.5 M Tris (pH 9.0). Using the assay cutoff (approximately 7.8 pg/ml), the standard assayed sera and the acid pretreated sera were positive in 65/291 (22.3%) and 167/291 (57.4%) of the samples, respectively. This difference between procedures was statistically significant (p < 0.0001) by McNemar chi 2. There was also a statistically significant difference between Walter Reed stages for p24 antigen quantification by ANOVA (p < 0.0001). We have demonstrated that the detection of p24 antigen may be significantly enhanced by acid pretreatment of sera which dissociates immune complexed antigen. We have also shown significant differences exist between Walter Reed stages for quantitative p24 antigen levels. Enhanced detection of p24 antigen may be important prognostically and may allow for the monitoring of antiretroviral therapy.
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PMID:Acidification modified p24 antigen capture assay in HIV seropositives. 140 37

Immunofluorescence studies were performed on the infection of monolayer cultures of immobilized MT-4 cells with human immunodeficiency virus type 1 (HIV-1). By using the anti-viral p24 monoclonal antibody, we could observe formation of foci of p24 antigen-positive cells within 3 to 4 days when the infection was initiated with a relatively small amount of the virus. Frequency of the focus formation was in proportion to the dose of input virus (ranging from 0.001 to 0.1 PFU/cell), which allowed us to apply this phenomenon to the assay of anti-HIV agents as well as to the estimation of relative infectivity of the virus stocks. When antiviral agents were added to the infected cultures, number of foci as well as the size of each focus was reduced in a concentration-dependent manner. The dose required for reducing the number of foci by 50% was calculated to be 6 ng/ml and 8 ng/ml for tunicamycin (TM) and azidothymidine (AZT), respectively. These values are comparable to those obtained by other current assay methods. In addition, focus reduction assay is also useful in searching for such antiviral agents that would inhibit or block the early step of viral replication cycle.
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PMID:Focus formation by the human immunodeficiency virus (HIV) in the immobilized MT-4 cell culture and its application to the evaluation of anti-HIV agents. 140 73

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children. 140 85

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of the acquired immunodeficiency syndrome (AIDS). Currently, no satisfactory treatment for this viral disease is available. Somatic gene therapy has been proposed as an alternative to conventional therapies. Several antiviral gene therapy approaches including ribozymes, antisense inhibition, and RNA-decoy strategies, as well as dominant-negative mutants of HIV-1 proteins (Gag, Tat, and Rev) have been suggested. To prove the concept of trans-dominant inhibition of HIV-1 replication, we transduced CEM cells with a retroviral vector encoding a dominant-negative rev gene. Amplification of integrase-specific proviral sequences from high molecular weight DNA indicated successful HIV-1 human T-lymphotropic virus type IIIB (HTLV-IIIB) infection of all cells. In contrast to CEM cells and CEM cells expressing the rev wild-type (wt) gene, infection of two CEM-RevM10 clones with HIV-1 did not result in the release of significant levels of p24 Gag antigen as measured by antigen capture assay, indicating a block in HIV-1 replication due to the presence of the trans-dominant Rev protein. Furthermore, the parental CEM cells as well as CEM cells expressing the Rev wt protein were effectively killed in the course of the HIV-1 infection, whereas all CEM cells expressing the RevM10 protein were unaffected in their growth rate.
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PMID:Inhibition of human immunodeficiency virus type 1 replication in human T cells by retroviral-mediated gene transfer of a dominant-negative Rev trans-activator. 140 15


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