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)

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

Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.
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PMID:Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates. 140 60

We have studied 65 children, born to HIV seropositive mothers, during the first quarter of life and afterwards every three-months. During this time, ten of the children (13%) became infected with the virus. The study of p24 antigen during the first 15 months of life showed an inverse relationship between the permanent presence of P24 antigen in the serum and the absence of anti-p24 antibodies. Since both markers were related to a bad prognosis, it is useful to carry-out the routine study of p24 antigen and its level in serum. Of the infections detected, 3 cases were early onset and the other 7 cases later onset. The three children from the first group died between 4 and 8 months of life, while the second group had a much more stable clinical situation. The children with early onset infections had T4 lymphocytes lower than 500 cell/mm3, detectable p24 antigen, and a fatal progression of the disease.
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PMID:[HIV infection in infants under 15 months of age. Value of the p-24 antigen as a prognostic marker]. 141 32

A two-site sandwich fluorescent-ELISA was optimized for the detection of HIV-1 p24 antigen produced by lymphoid cells infected with HIV-1 in vitro. To improve the sensitivity of the ELISA, a combination of streptavidin-beta-galactosidase and a fluorogenic substrate (4-methylumbelliferyl-beta-D-galactopyranoside) was employed for the enzymatic detection stage. Using recombinant p24 as standard antigen, a two-step assay detected as little as 0.7 pg/ml (3.10(-14) M) with an upper limit of 10,000 pg/ml. This detection range (approx. 50-70-times greater than ELISAs using a chromogenic detection) permitted an accurate and straightforward quantitation of p24 in culture supernatants. Overall, the fluorescent-ELISA had increased detectability, sensitivity and efficiency over existing ELISAs for HIV-1 p24.
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PMID:Development of a sensitive ELISA for HIV-1 p24 antigen using a fluorogenic substrate for monitoring HIV-1 replication in vitro. 143 56

The molecular mechanisms involved in the replication of human immunodeficiency virus type 1 (HIV-1) may differ in various cell types and with various exogenous stimuli. Astrocytic glial cells, which can support HIV-1 replication in cell cultures and may be infected in vivo, are demonstrated to provide a cellular milieu in which TAR mutant HIV-1 viruses may replicate. Using transfections of various TAR mutant HIV-1 proviral constructs, we demonstrate TAR-independent replication in unstimulated astrocytic cells. We further demonstrate, using viral constructs with mutations in the tat gene and in the nuclear factor kappa B (NF-kappa B)-binding sites (enhancer) of the HIV-1 long terminal repeat, that TAR-independent HIV-1 replication in astrocytic cells requires both intact NF-kappa B moiety-binding motifs in the HIV-1 long terminal repeat and Tat expression. We measured HIV-1 p24 antigen production, syncytium formation, and levels and patterns of viral RNA expression by Northern (RNA) blotting to characterize TAR-independent HIV-1 expression in astrocytic glial cells. This alternative regulatory pathway of TAR-independent, Tat-responsive viral production may be important in certain cell types for therapies which seek to perturb Tat-TAR binding as a strategy to interrupt the viral lytic cycle.
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PMID:TAR-independent replication of human immunodeficiency virus type 1 in glial cells. 143 28

In this article the literature about didanosine, an antiretroviral drug, is reviewed. The mechanism of action, biochemical pharmacology, pharmacokinetics, and clinical results of phase-I trials are discussed. Serious adverse effects such as pancreatitis and peripheral neuropathy have occurred in these trials. An antiretroviral effect was observed in terms of an increase in CD4+ lymphocytes and a decrease in p24 antigen levels in HIV-infected individuals. Didanosine seems to be a promising drug against HIV infection, but knowledge about its clinical efficacy is scanty.
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PMID:Didanosine, a new antiretroviral drug. A review. 143 13

Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have designed a hairpin ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence (at nucleotides +111/112 relative to the transcription initiation site). The ribozyme was tested in vitro and gave efficient and specific cleavage of RNA containing the leader sequence. To test the antiviral efficacy of this ribozyme, we have cotransfected into HeLa cells HIV-1 proviral DNA and a plasmid expressing the ribozyme from the human beta-actin promoter. HIV-1 expression was inhibited as measured by p24 antigen levels and reduced Tat activity. The antiviral effect of the ribozyme appears to be specific and results from directed RNA cleavage; activity requires both a target sequence and a functional RNA catalytic center. These results suggest that this HIV-1-directed hairpin ribozyme may be useful as a therapeutic agent.
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PMID:Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. 143 80

Three modifications of ELISA test system for HIV antigen detection are described. They are based on IgG from HIV-1 and HIV-2-infected human sera and monoclonal antibodies against HIV-1 p24 used as immunosorbents. The peroxidase/anti-HIV-IgG conjugate was used in all the test systems. A possibility of quantitative detection of viral antigen in native culture fluids, lysates, and purified virus preparations was demonstrated. The test system for HIV-1 antigen detection cannot be used for HIV-2 antigen detection and vice versa. The diagnostic value of HIV-1 p24 antigen detection consists in the possibility of earlier AIDS identification and monitoring of the disease at various stages. The sensitivity of "p24" assay is 0.5 ng/ml.
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PMID:[The detection and quantitative determination of antigens to the human immunodeficiency virus types 1 and 2]. 144 38

We have studied 70 children, born to HIV seropositive mothers, since the first trimester of life and every three months thereafter. The virological markers we used in the diagnosis included: 1) p24 antigen detection. 2) Autochthonous production of antibodies detected by Western Blot technique. 3) HIV isolation. 4) Specific determination of IgM antibodies. In infected children under 15 months of age, p24 antigen was positive in 78%, HIV was isolated in 75% and autochthonous production of antibodies occurred in 50%. IgM specific antibodies were detected in 92%, but these were also detected in the 33% of the children who seroreverted. In seroreverted children, the other three virological markers were negative. The problems due to the low sensitivity in p24 antigen detection, HIV isolation and the detection of autochthonous production of antibodies, as well as the low specificity of the IgM detection, means that it is necessary to simultaneously use several techniques in the diagnosis of these children.
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PMID:[Early diagnosis of HIV infection in children born to seropositive mothers]. 144 20


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