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

In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.
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PMID:Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals. 137 10

In an attempt to better understand the role of endothelial cells during HIV-1 infection, we report a virological and ultrastructural study on isolated endothelial cells from human adipose tissue, infected by HIV-1 in vitro. Supernatants from cultures showed the presence of p24 antigen and reverse transcriptase activity starting two days after HIV inoculation. A significant decrease of viral rescue was observed in cycloheximide treated cells confirming a de novo synthesis of viral products. SEM analysis individualized several surface slender projections and interdispersed virus-like particles in the infected cells. Furthermore, transmission electron microscopy (TEM) results showed cellular aspects of HIV phagocytosis and virus budding, suggesting that endothelial cells may represent a CD4 negative cell target of HIV-1 infection.
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PMID:Human immunodeficiency virus type-1 (HIV-1) infection of endothelial cells in vitro: a virological, ultrastructural and immuno-cytochemical approach. 137 12

A number of non-human-immunodeficiency-virus (HIV) type 1 disorders are associated with CD4+ T-cell deficiency and dysfunction. However, the etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains unclear. Human intracisternal retroviral (HICRV) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally, the HICRV is distinct from HIV-1, HIV-2, human T-lymphotropic virus (HTLV) type I, and HTLV-II. Supernatants of activated mononuclear cells showed significant reverse transcriptase activity that was predominantly Mn2+ dependent. The patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-II proviruses as demonstrated by the lack of amplification by PCR. Also, the patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-II and for HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV as demonstrated by Western blot. Similar HICRV particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from the patient's daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1, HIV-2, HTLV-I, and HTLV-II.
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PMID:Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency. 138 Jan 69

Down-regulation of Epstein-Barr virus (EBV) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. This article reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen, and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been shown previously to have antiproliferative effects, now are shown to reduce HIV-1 replication. DHEA or synthetic analogs of DHEA could provide an alternative and/or adjuvant for HIV-1 infection.
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PMID:Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. 138 Dec 6

Reverse transcriptases contain a highly conserved YXDD amino acid motif believed to be important in enzyme function. The second amino acid is not strictly conserved, with a methionine, valine or alanine occupying the second position in reverse transcriptases from various retroviruses and retroelements. Recently, a 3.5-A (0.35-nm) resolution electron density map of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase positioned the YMDD motif within an antiparallel beta-hairpin structure which forms a portion of its catalytic site. To further explore the role of methionine of the conserved YMDD motif in HIV-1 reverse transcriptase function, we have substituted methionine with a valine, alanine, serine, glycine, or proline, reflecting in some cases sequence motifs of other related reverse transcriptases. Wild-type and mutant enzymes were expressed in Escherichia coli, partially purified by phosphocellulose chromatography, and assayed for the capacity to polymerize TTP by using a homopolymeric template [poly(rA)] with either a DNA [oligo(dT)] or an RNA [oligo(U)] primer. With a poly(rA).oligo(dT) template-primer, reverse transcriptases with the methionine replaced by valine (YVDD), serine (YSDD), or alanine (YADD) were 70 to 100% as active as the wild type, while those with the glycine substitution (YGDD) were approximately 5 to 10% as active. A proline substitution (YPDD) completely inactivated the enzyme. With a poly(rA).oligo(U) template-primer, only the activity of mutants with YVDD was similar to that of the wild type, while mutants with YADD and YSDD were approximately 5 to 10% as active as the wild-type enzyme. The reverse transcriptases with the YGDD and YPDD mutations demonstrated no activity above background. Proviruses containing the reverse transcriptase with the valine mutation (YVDD) produced viruses with infectivities similar to that of the wild type, as determined by measurement of p24 antigen in culture supernatants and visual inspection of syncytium formation. In contrast, proviruses with reverse transcriptases containing the YADD and YSDD mutations were less infectious than wild-type virus. These results point to the critical role of methionine of the YMDD motif in the activity of HIV-1 reverse transcriptase and subsequent replication potential of the virus.
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PMID:In vitro enzymatic activity of human immunodeficiency virus type 1 reverse transcriptase mutants in the highly conserved YMDD amino acid motif correlates with the infectious potential of the proviral genome. 138 71

Peripheral blood mononuclear cells from 12 asymptomatic patients infected with immunodeficiency virus (HIV) and 4 patients with AIDS were analyzed before and during therapy with zidovudine for T helper cell (Th) function. Th function improved by more than fourfold to one or more of three stimuli tested in 9 (75%) of 12 asymptomatic patients on zidovudine therapy and in 3 of 4 patients with AIDS. Only 6 (7.4%) of 80 untreated HIV-infected control patients showed spontaneous improvement in Th function (P less than 10(-6)). Improved Th function was detected as early as 5 weeks into therapy in 6 patients and continued to be evident for greater than 1 year after start of therapy in 6 patients and for greater than 2 years in 2 patients. No correlation was observed between improved Th function and changes in CD4+ or CD8+ cell numbers or in levels of serum HIV p24 antigen or beta 2-microglobulin. These results suggest inclusion of in vitro Th function as a useful marker in determining the efficacy of antiretroviral drug therapy of HIV-infected patients.
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PMID:Reconstitution of long-term T helper cell function after zidovudine therapy in human immunodeficiency virus-infected patients. 138 95

Sequential plasma samples obtained from 16 individuals who seroconverted were tested for the presence of antibody to human immunodeficiency virus type 1 (HIV-1) by an antigen conjugate enzyme immunoassay (EIA) and a conventional antibody conjugate assay. In 11 of these individuals, the antigen conjugate assay detected antibody to HIV-1 2 to 11 days (mean, 5.5 days) earlier than the antibody conjugate assay. In 11 individuals, HIV-1 p24 antigen was detected a median of 6.5 days (range, 3 to 14 days) prior to positivity by the antigen conjugate EIA. Using class-specific probes, we determined the profiles of immunoglobulin M (IgM), IgG, and IgA antibodies for each individual and correlated these profiles with the EIA signals from both assays. In general, the appearance of IgM exhibited a peak at about 1 week postseroconversion, which was followed by gradually declining levels. Absorbance levels for IgG antibody, however, rose steadily and reached a plateau after 3 to 5 weeks. The levels of IgA were generally low and variable. In contrast to the progressive increase in EIA absorbance observed by the antibody conjugate assay, the antigen conjugate assay displayed a rapid early rise in absorbance which generally coincided with the transient expression of IgM antibody. The subsequent gradual increase coincided with rising levels of IgG. Because the configuration of the antigen conjugate EIA allows for an increased sensitivity for IgM compared with that for other classes of immunoglobulins, these results suggest that earlier detection of antibody to HIV-1 is due to the detection of IgM antibody during the early phase of seroconversion.
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PMID:Early detection of antibody to human immunodeficiency virus type 1 by using an antigen conjugate immunoassay correlates with the presence of immunoglobulin M antibody. 140 Oct 2

Mycoplasma fermentans incognitus has attracted much interest either as a cofactor for the progression of AIDS or as a pathogenic agent in non-AIDS-related diseases (S.-C. Lo, M. S. Dawson, P. B. Newton III, M. A. Sonoda, J. W.-K. Shih, W. F. Engler, R. Y.-H. Wang, and D. J. Wear, Am. J. Trop. Med. Hyg. 41:364-376, 1989; S.-C. Lo, M. S. Dawson, M. Wong, P. B. Newton III, M. A. Sonoda, W. F. Engler, R.Y.-H Wang, J. W.-K. Shih, H. J. Alter, and D. J. Wear, Am. J. Trop. Med. Hyg. 41:601-616, 1989; S.-C. Lo, J.W.-K. Shih, N.-Y. Yang, C.-Y. Ou, and R. Y.-H. Wang, Am. J. Trop. Med. Hyg. 40:213-226, 1989). In the present study, the genetic and serologic properties of the incognitus strain and other M. fermentans strains were compared. Furthermore, the replication of human immunodeficiency virus type 1 (HIV-1), determined by reverse transcriptase activity and HIV-1 p24 antigen level, in peripheral blood mononuclear cells was evaluated after stimulation with mycoplasma cell lysates. The psb-2.2 viruslike infectious agent DNA probe, used to identify the incognitus strain in the tissues of AIDS and non-AIDS patients by Lo et al. (Am. J. Trop. Med. Hyg. 41:364-376 and 40:213-226, 1989), showed reaction patterns similar to those of two M. fermentans strains isolated from cell cultures but not to that of the type strain PG18. Restriction enzyme patterns of the incognitus strain with EcoRI and HindIII were also similar to those of M. fermentans strains isolated from cell cultures. There were no remarkable differences in the immunoblot profiles between the incognitus strain and the other M. fermentans strains. These results suggest that the incognitus strain is not a unique strain among M. fermentans strains. Further, cell lysates of each M. fermentans strain could also enhance the replication of HIV-1 to a level similar to that of the incognitus strain as determined by the reverse transcriptase activity and the amount of the p24 antigen.
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PMID:Evidence that Lo's mycoplasma (Mycoplasma fermentans incognitus) is not a unique strain among Mycoplasma fermentans strains. 140 Oct 12

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

To promote progress in the research and development of early diagnostic tests for HIV in young children an international workshop was held on January 17-18, 1992, in Siena, Italy. Experts on pediatric AIDS, diagnostic retrovirology, and immunodiagnosis discussed and summarized the state-of-the-art and made recommendations for general application of several tests and further evaluation and continued research for other candidate tests. From the discussions it was clear that the field has advanced beyond the time when it was necessary to wait until the infant reached 18 months of age before attempting the diagnosis with conventional serologic tests for HIV. About half of infected infants can now be identified at birth, approximately 90% by 3 months of age, and almost all by 6 months of age using HIV culture and polymerase chain reaction assays. IgA antibody tests and p24 antigen tests have also proved useful, although they are not as sensitive in newborn infants. The fact that HIV can be detected in only one-half of infected infants at the time of birth points to the need for further research on the timing of transmission and the natural history of perinatally acquired HIV infection to understand the limitations of current early diagnostic tests and to develop new approaches to overcome these problems.
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PMID:Report of a consensus workshop, Siena, Italy, January 17-18, 1992. Early diagnosis of HIV infection in infants. 140 48


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