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

Conflicting data have been reported on ability of 3'-azido-3'-deoxythymidine (AZT) to protect mononuclear phagocytes from HIV-1 infection. We compared the antiviral potency of AZT in three types of primary human mononuclear phagocytes: peripheral blood monocytes, monocyte-derived macrophages (in vitro differentiated) and alveolar macrophages (in vivo differentiated). To establish highly-productive virus infection, purified cells (greater than 99%) from healthy donors were challenged with the macrophage-tropic HTLV-IIIBa-L strain at input multiplicities ranging from 0.05 to 20 TCID50 per cell. AZT (0.1 nM-10 microM) was added immediately after infection and either continued for the duration of the experiment or stopped 1-7 days after infection. The kinetics of HIV-1Ba-L replication were assessed by measuring p24 antigen production on days 4-28 post-infection. Continuous treatment with AZT reproducibly inhibited viral replication in a concentration-dependent manner in all three cell types. The IC90 of AZT was 0.04 microM in blood monocytes, 0.009 microM in monocyte-derived macrophages, and 0.0001 microM in alveolar macrophages (mean of 3-4 donors for each cell type). AZT was not cytotoxic at less than 10 microM as assessed by cell viability, cell protein, and interferon-gamma-activated H2O2-release. In experiments in which AZT treatment was stopped after infection, viral replication resumed after a lag of 7-14 days and increased exponentially toward control levels. This occurred despite initial inhibition of virus production to below the limit of p24 detection (approximately 50 pg/ml). These results indicate that AZT is a potent inhibitor of HIV-1 replication in primary mononuclear phagocytes regardless of the stage of cell differentiation, and that AZT is most active in tissue (alveolar) macrophages. AZT does not irreversibly block infection of mononuclear phagocytes, however, as viral replication resumes after removal of AZT.
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PMID:Anti-HIV-1 activity of 3'-azido-3'-deoxythymidine (AZT) in primary mononuclear phagocytes. 144 21

Thirty-six sexually active couples serologically discordant for human immunodeficiency virus, type 1 (HIV-1), within the Baltimore Multicenter AIDS Cohort Study (MACS) were assessed to determine whether evidence of HIV-1 infection could be detected in the HIV-1-antibody-negative partners and whether factors associated with lack of transmission of HIV from the seropositive to the seronegative partner could be ascertained. Six HIV-1 seropositive couples and 18 seronegative couples were followed concurrently for comparison. None of the seropositive subjects had an AIDS-defining illness at entry into the study, and all subjects were followed for 1 year. A separate evaluation of unprotected anal receptive and insertive intercourse between discordant couples indicated high-risk activities for a median of 40 months, as reported by the HIV seropositive partner. Despite this finding, none of the HIV-1 seronegative men in discordant couples had evidence of HIV-1 infection by viral culture, p24 antigen testing, or polymerase chain reaction for HIV-1 DNA. Discordant seronegatives and seropositives did not differ from concordant seronegatives and seropositives in numbers of circulating CD4, CD8, and natural killer lymphocytes or in prevalence of antibodies to herpes simplex virus, type 1, Epstein-Barr virus, or cytomegalovirus, except that discordant seronegative men were less likely than their seropositive partners to have antibodies to herpes simplex virus, type 2. The reason for the apparent lack of HIV-1 infection in seronegative discordant individuals remains unexplained and did not appear to be associated with type of sexual activity, T-lymphocyte subsets or natural killer cells, or early stage of HIV-1 disease.
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PMID:Longitudinal study of homosexual couples discordant for HIV-1 antibodies in the Baltimore MACS Study. 145 31

Transient expression of HIV-1 p24 antigen was observed in eosinophils acutely infected with the HTLV-IIIB strain of HIV-1. PCR analysis of eosinophils isolated from 18 seropositive individuals showed HIV-1 sequences to be present in 2 subjects. These data suggest that eosinophils may act as host cells for HIV-1.
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PMID:Eosinophils as host cells for HIV-1. 145 97

An in vitro model has made it possible to demonstrate HIV transmission from infected lymphocytes to placental trophoblast cells via endocytosis. Upon addition to cultured trophoblast cells (BeWo), chronically HIV-infected lymphocytic cells (MOLT-4) adhered to the epithelial cells via a complex of newly induced microvilli. Though viruses were infrequently seen in the infected lymphocytic cell line, mature virions appeared promptly and profusely in the interstices between the interdigitating microvilli of the two cell types. Virions appeared to bud from the lymphocyte donor cells at the point of cell-to-cell contact and were rapidly taken up by the trophoblast cells via an endocytic mechanism involving coated pits, endosomes, and lysosomes. Electron microscopic observations suggest that HIV may later escape into the trophoblast cytoplasm by fusing with the endosome membrane or by lysing the lysosome membrane. Coincubation for 1 h was sufficient to establish HIV infection in the trophoblast cell line. Four weeks after thoroughly washing out the donor lymphocytic cells, HIV RNA was demonstrated in clusters of BeWo cells by in situ hybridization, and p24 antigen was localized with immunocytochemistry. Soluble CD4 did not block infection as measured by p24 ELISA. The HIV infection was productive and chronic as demonstrated by cocultivating the BeWo cells with indicator lymphocytes 4 weeks after the initial infection. This study, demonstrating a mechanism of HIV transmission, expands upon previous observations that trophoblast cell lines lacking the CD4 viral receptor can nevertheless be infected by HIV and can support productive infection.
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PMID:HIV-1 infection of the trophoblast cell line BeWo: a study of virus uptake. 145 13

Adult T-cell leukemia (ATL)-derived factor (ADF) is a multifunctional protein homologous to thioredoxin (TRX) with co-cytokine and thiol-dependent reducing activities. ADF/thioredoxin production is enhanced in T cells transformed by HTLV-I. We have examined the effect of HIV-1 infection on ADF/TRX expression using specific antibody against ADF/TRX. Lymph nodes from 5 AIDS and 1 AIDS-related complex (ARC) patients were examined. As a control, 8 HIV noninfected lymph nodes, including 3 cases with hyperplasia, were also examined. Immunohistopathological studies using normal HIV noninfected lymph nodes showed that ADF/TRX high-producer (ADFh) cells were macrophages and cells with dendritic morphology in the paracortical area. Abundant ADFh cells were observed in HIV noninfected hyperplastic lymph nodes. The number of ADFh cells was low in hyperplastic lymph nodes from an ARC patient. All of the lymph nodes of 5 AIDS cases were atrophic and the number of ADFh cells were extremely low. To verify these histochemical studies, we examined the effect of in vitro HIV infection on ADF/TRX expression in HTLV-I (+) T-cell lines. Western blot analysis showed that a reduction of ADF/TRX in HIV-1-infected SKT-1B and MT-2 cells, and the reduction inversely correlated with p24 antigen level. On the basis of the above in vivo and in vitro findings, we imply that the levels of ADF/TRX were down-regulated by HIV-1 infection and that the down-regulation may play a role for pathophysiology of HIV-infected individuals.
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PMID:Dysregulation of adult T-cell leukemia-derived factor (ADF)/thioredoxin in HIV infection: loss of ADF high-producer cells in lymphoid tissues of AIDS patients. 145 16

HIV-1 p24 antigen was detected in 554 sera (509 from HIV-1 seropositive individuals and 45 sera from seronegative controls) using a conventional method with acid pretreatment of the sample in order to separate the p24 antigen/anti-p24 antibody immune complexes. In asymptomatic individuals there was a substantial increase in antigen detection (48.2% vs 8.4%). Similar results were also observed in ARC (59.1% vs 12.2%) and AIDS patients (85.7% vs 37.1%). It can be concluded that the acid treatment improves the sensitivity of conventional techniques to detect HIV-1 p24 antigen.
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PMID:Improved detection of HIV p24 antigen in serum after acid pretreatment. 146 28

A sensitive assay was developed for in vitro evaluation of anti-HIV agents in monocyte-macrophage cells (M/M) (a crucial target of HIV in the body). Monocyte-macrophage cells are usually poorly sensitive to the cytopathic effect induced by HIV. However, when fresh adherent monocyte-macrophage cells are cultured at relatively high density in the presence of macrophage-colony stimulating factor (M-CSF), they undergo cytolysis and die in 2-3 weeks. HIV-mediated cell-killing can thus be assessed with a method based on the reduction of the yellow colored 3-(4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by metabolically active cells to a blue formazan, which can be measured spectrophotometrically. HIV-mediated cytopathic effect of M-CSF-exposed monocyte-macrophage cells was consistently achieved in all experiments performed under the conditions described herein. Anti-HIV activity of zidovudine (AZT) was also comparatively evaluated in M-CSF- and normal monocyte-macrophage cells both using the MTT assay and by measuring HIV-p24 antigen production in supernatants of monocyte-macrophage cells cultures, and similar results obtained with both methods. These results support the use of this colorimetric assay for broad screening of anti-HIV agents in monocyte-macrophage cells.
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PMID:A tetrazolium-based colorimetric assay for quantification of HIV-1-induced cytopathogenicity in monocyte-macrophages exposed to macrophage-colony-stimulating factor. 147 34

Antibodies directed against the third hypervariable loop-domain (V3 loop) of human immunodeficiency virus type 1 (HIV-1) gp120 inhibit the infection by HIV-1 in a type-specific manner without interfering with the binding of gp120 to CD4. Previous studies demonstrated that soluble CD4 (sCD4) induced the dissociation of gp120 with gp41 and caused conformational changes within the envelope oligomer. We report changes in the binding and neutralizing activity of a monoclonal antibody against the V3 loop after sCD4 binding to gp120. Flow cytometry revealed that a type-specific neutralizing monoclonal antibody against V3 loop of HTLV-IIIB, 0.5 beta, reacted with HTLV-IIIMN-infected cells after exposure to sCD4. When the sCD4-treated HTLV-IIIMN infected cells were analyzed by two-color flow cytometry, most of the CD4-bearing cells were 0.5 beta-positive, indicating that this reactivity of 0.5 beta was associated with the binding of sCD4 to the infected cells. To determine the cross-neutralization by 0.5 beta after exposure to sCD4, HTLV-IIIMN viruses pretreated with sCD4 were used to infect susceptible target cells. The addition of 0.5 beta significantly reduced the p24 antigen production (66.1 +/- 5.9 pg/ml) compared with a control murine IgG (221.3 +/- 15.3 pg/ml). In contrast, no significant reduction in the p24 antigen production was observed by adding the HTLV-IIIMN neutralizing monoclonal antibody, mu 5.5, (209.9 +/- 15.0 pg/ml). Taken together, these results suggest that sCD4/gp120 binding could induce conformational/antigenic changes within the V3 loop that result in the induction of cross-reactivity and cross-neutralizing activity of a type-specific monoclonal antibody.
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PMID:Changes in the reactivity and neutralizing activity of a type-specific neutralizing monoclonal antibody induced by interaction of soluble CD4 with gp120. 149 53

Cumulative data on serological testing of newborns and infants have shown that (i) maternal and newborn anti-HIV-1 IgG titers are high at delivery, which may explain the persistence of antibody in the infants of seropositive mothers; (ii) in some situations, serial HIV-1 antibody testing may identify infected infants; and (iii) detection of anti-HIV-1 IgA or IgM is specific for infection but the sensitivity of this assay may be compromised in certain situations, such as when infected infants are hypogammaglobulinemic or when the rise and fall of HIV-1-specific IgM synthesis following acute infection has been completed before delivery of the infant. Cumulative data on PCR, viral culture, and tests for antigen in newborns and infants have shown that (i) among all age groups, viral culture is probably the most specific test available for detection of HIV-1, as PCR and the p24 antigen test may (though rarely) give false-positive results; (ii) the sensitivity of these tests increases in the order of antigen, culture, and PCR, with relatively insensitive results in the first 3 months of life for all of these tests; (iii) the sensitivity of all of these tests improves and approximates 90 to 100% when infants over 6 months of age are tested; and (iv) data regarding the sensitivity, specificity, and usefulness of these virological assays in infants under 3 months of age are very scant and inconclusive.
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PMID:Laboratory methods for early detection of human immunodeficiency virus type 1 in newborns and infants. 149 66

CD4 is the principal receptor for the human immunodeficiency virus (HIV). We have isolated and studied CD4-expressing tumor cell clones made by expressing CD4 in the T-cell tumor line HSB. Two clones, one designated HSBCD4, a clone expressing low levels of CD4, and the other, HSB10xCD4, a high-expresser CD4+ clone, were studied for their ability to bind and replicate HIV. In contrast to many other CD4+ cells that down-modulate CD4 following HIV infection, the HSB10xCD4 clones continued to express high levels of surface CD4 following infection with HIV. Unlike infection of HSBCD4 or many other human CD4+ cells, HIV infection of HSB10xCD4 clone was short lived: p24 antigen, provirus, or coculturable virus was present for less than 14 days following infection with several strains of HIV-1 or with HIV-2. When infection was initiated by transfection of proviral DNA, high and low CD4 expressers initially produced p24 antigen at approximately the same level. However, high CD4 expressers produced coculturable virus only during the first few days following transfection, whereas low CD4 expressers transfected with HIV continued to produce virus beyond 6 weeks. Monoclonal antibody-mediated down-modulation of CD4 surface expression on HSB10xCD4 clones permitted these formerly HIV-resistant cells to become persistently infected with HIV. Thus, high concentrations of CD4 on the surface of an HIV-infected cell prevent persistent HIV infection of CD4+ cells.
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PMID:High level of surface CD4 prevents stable human immunodeficiency virus infection of T-cell transfectants. 150 Dec 85


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