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

The effect of the antileukemic and anti-HIV agent avarol on the lymphoid system was studied both in vitro and in vivo. Radioactively labelled avarol ([3H]-dihydroavarol) was found to accumulate in vitro in the cytoplasmic compartment primarily of T-lymphocytes and not of B-lymphocytes. Avarol increased significantly the IgG and IgM production by cultures of human lymphoid cells (unseparated) in vitro and slightly the number of plaque forming cells in vivo in spleen of mice. Moreover, a pretreatment of mice with avarol resulted in a higher [3H]-dThd incorporation rate in both macrophage-containing and macrophage-depleted lymphocyte cultures in vitro. The stimulatory influence of avarol on humoral immune responses is not accompanied by a change of the antibody-mediated hypersensitivity reaction, as measured by the Arthus reaction. No significant influence of avarol on the cellular immune system in vivo (rats or mice) was found, as taken from studies on delayed-type hypersensitivity reactions to sheep red blood cells and to oxazolone. The in vitro and animal data indicate that avarol combines useful properties (anti-HIV efficiency in vitro and augmentation of humoral immune responses) to consider it as a potential anti-AIDS agent.
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PMID:Influence of the antileukemic and anti-human immunodeficiency virus agent avarol on selected immune responses in vitro and in vivo. 355 7

HIV-infected patients exhibit defects in B cell differentiation and in the IL-6 response of B cells, in association with autoantibody formation against T cells. These autoantibodies have been implicated as important factors in the development of immunodeficiency disease. As the restoration of defective B cell responses might prevent autoantibody formation and the resulting immunosuppression, we studied whether in vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4) or recombinant IL-6 (rIL-6) might restore the response of B cells of HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4 HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at CDC stage IV, and 6 healthy controls were tested in Staphylococcus aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen (PWM)-stimulated allogeneic B and T cell cocultures. B cell differentiation was assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG and IL-6 in culture supernatants. In vitro application of rIL-6 resulted in suppression of both elevated unstimulated and mitogen-stimulated B cell responses in a dose-dependent manner which was in part due to feedback inhibition. PWM- and SAC-I-stimulated IgG and IgM responses, respectively, could be restored after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in HIV-positive patients. Addition of rIL-4 to cultures resulted in suppression of both unstimulated and mitogen-stimulated IL-6 secretion and B cell responses. Severely depressed B cell responses in CDC IV patients were not significantly affected by cytokine application. These results indicate that defective Ig responses in HIV-negative patients may be restored by rIL-2 treatment whereas HIV-induced B cell defects are not corrected by supply of T cell help or cytokines promoting B cell growth and differentiation.
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PMID:In vitro cytokine treatment of B cell defects in HIV-infected hemophilia patients. 748 89

R82913 and R86183, two derivatives of tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO), were found to potently and selectively inhibit the replication and cell killing effects of a panel of biologically diverse laboratory and clinical strains of HIV-1. The two compounds exhibited significant activity in all human cell lines tested, as well as in fresh human peripheral blood lymphocytes and macrophages. One of these two compounds (R82913) was found to significantly inhibit the replication of a murine retrovirus (Rauscher murine leukemia virus) in both UV-XC plaque formation and virus yield reduction assays. R86183, despite differing from R82913 only in the positioning of a single chlorine molecule, was not active against the murine retrovirus but was 10-fold more potent in inhibiting HIV-1 replication. Combination antiviral assays with other reverse transcriptase inhibitors, including AZT, ddC, and carbovir, yielded synergistic anti-HIV activity with both TIBO derivatives. Additive to slightly synergistic results were obtained in combinations with ddI and phosphonoformic acid whereas additive to antagonistic activity was detected in combination with dextran sulfate.
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PMID:Differential antiviral activity of two TIBO derivatives against the human immunodeficiency and murine leukemia viruses alone and in combination with other anti-HIV agents. 750 23

Studies in ungulate lentivirus systems clearly indicate that neutralization escape variants emerge over time in chronically infected animals. Studies in the EIAV system, in particular, have provided strong evidence that the humoral branch of the immune system is at least one selective force acting on an array of viral variants. In previous studies with the ungulate lentiviruses, molecularly cloned virus was never used, and plaque-purified virus was only sometimes used; the genetic determinants responsible for antigenic variation and immune selection were not determined. While molecular clones are available for HIV-1, immune selection studies have been hampered in this system by the fact that HIV-1 is infectious only for chimpanzees, which do not develop disease and are available in only limited numbers. Experiments on immune selection in humans are generally complicated by lack of knowledge on the time of infection and the genetic make-up of the infecting virus. Our studies on SIV immune selection summarized in this review provide definitive evidence that neutralization-resistant variants emerge in an individual during persistent infection by primate lentiviruses. By cloning viral envelope genes from rhesus monkeys over time and obtaining sequential serum samples from them, we have been able to study not only the evolution of envelope sequences but also the emergence of neutralization-resistant variants. Reciprocal neutralization studies were performed using parental and variant specific sera, and immune selection was demonstrated using molecularly cloned virus of defined sequence. During the course of persistent infection with SIV and HIV, there is clear selective pressure for change in discrete variable regions of envelope. The host neutralizing antibody response appears to be at least one of the selective forces driving sequence change in envelope since one result of the sequence variation is the emergence of neutralization escape mutants. This indicates that neutralizing antibodies do serve to limit HIV and SIV replication during the lengthy asymptomatic stage of infection. The coincidence of neutralization domains of HIV and/or SIV with variable regions V1, V2, V3, V4, V5, and V6 suggests a direct relationship between neutralization domains and the emergence of sequence variants. However, different selective forces may be responsible all or in part for driving sequence changes in some variable domains (summarized in Table 2). For example, alterations in cell and/or tissue tropism may be responsible at least in part for driving change in V3 and the cytotoxic T-lymphocyte response may be responsible for driving change in the signal peptide (V0; Henderson et al. 1992; Wei and Cresswell 1992).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Envelope sequence variation, neutralizing antibodies, and primate lentivirus persistence. 752 31

The aims of this study were to compare the prevalence of suspected periodontal pathogens in subgingival plaque from 29 HIV seropositive and 27 control subjects and to determine the association of these bacteria with periodontal destruction. Subgingival plaque was collected from the mesiobuccal sites of all teeth, except 3rd molars. Bacteria were identified and enumerated using non-isotopic whole chromosomal DNA probes and a colony lift method. At baseline, HIV seropositive subjects had significantly higher mean % of Porphyromonas gingivalis than control subjects. This difference could be attributed to a subgroup of HIV seropositive subjects with widespread attachment loss. No correlations were observed between the mean %s of DNA probe species and mean attachment loss, CD4 and CD8 T lymphocyte counts or CD4: CD8 ratio. No significant microbiological differences were detected between active and control sites in HIV seropositive subjects on a longitudinal basis. There appeared to be an inverse relationship between the mean %s of P. gingivalis and V. parvula, with respect to progression of HIV infection. The ability of microbiological parameters to predict site-specific breakdown in HIV seropositive subjects requires further investigation.
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PMID:Comparison of periodontal disease in HIV seropositive subjects and controls (II). Microbiology, immunology and predictors of disease progression. 756 Feb 41

A 49-year-old Japanese male who had been imprisoned for five years then lived with other men complained of fever, constitutional symptoms and a 12 kg weight loss over four-month period. He was referred to us as his gastric washings were positive for acid-fast bacilli (AFB). Chest X-ray showed patchy, infiltrative small shadows primarily in the right upper lung field without hilar adenopathy. Before transfer to our hospital, tuberculosis chemotherapy composed of SM, INH, RFP and PZA was initiated. Over the next three weeks, fever dropped, and the above described abnormal shadows on the chest X-ray improved, leaving small cystic lesions. Although a sputum smear was negative for AFB, M. tuberculosis was isolated from cultured samples and sensitive to all standard anti-tuberculous drugs. AFB were also demonstrated on a touch imprint of biopsied cervical lymph nodes. Sputum samples turned negative one month later both on smear and culture. Moreover, high fever developed and another abnormal shadow indicative of Pneumocystis carinii (PCP) appeared in the left lung field one month after the admission. White plaque was noted in the oral cavity. Dark red nodules were observed on the upper extremities and chest wall, and diagnosed histologically as Kaposi's sarcoma. Serologic testing for HIV was positive both by PA and Western blot methods, thus AIDS was diagnosed according to the CDC surveillance case definition for AIDS with the diagnosis of tuberculosis. The patient died of wasting syndrome on the 90th hospital day. On autopsy, small thin-walled cavities were observed in the right upper lung, correlating with earlier X-ray and CT findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case report of the atypical tuberculosis associated with AIDS]. 756 52

We have attempted to relate genetic recombination involving human immunodeficiency virus type 1 (HIV-1) to multiple drug resistance by using PEG to fuse subclones of U937 cells that carried HIV-1 recombinants resistant to either 3' -azido-3'-deoxythymidine (AZT) or the (--) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). The parental viruses employed contained well-defined mutations in the pol gene. Fused cells were co-cultured with the MT4 lymphocyte cell line for virus amplification to yield progeny that, in some cases, possessed different patterns of drug resistance from parental viruses. Mutational analyses were performed by PCR to substantiate these observations, which were also confirmed by direct sequencing of single strands of DNA segments, obtained from plaque-purified viruses. These studies indicate that viral recombination had occurred, and establish a theoretical basis on which to conclude that the acquisition of multiple drug resistance on the part of HIV-1 may be related to its ability to promote cell fusion.
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PMID:Possible involvement of cell fusion and viral recombination in generation of human immunodeficiency virus variants that display dual resistance to AZT and 3TC. 759 65

Triciribine (TCN) and its 5'-monophosphate (TCN-P) are novel tricyclic compounds with known antitumor activity; TCN-P is currently in phase II human clinical trials. We now report that these compounds have potent and selective activity against HIV-1 and HIV-2. Using a syncytial plaque assay, TCN and TCN-P were active against HIV-1 at 0.01-0.02 microM and had differential selectivities of 2250 and 1900, respectively, compared to 1850 for AZT. In contrast, TCN and TCN-P had minimal selectivity against human cytomegalovirus (50 and 27, respectively). TCN and TCN-P markedly inhibited HIV-1-induced p24 core antigen production, reverse transcriptase, and infectious virus production in a dose-dependent manner using HIV-1 acutely infected CEM-SS, H9, and persistently infected H9IIIB and U1 cells. In acutely infected PBL cells, TCN and TCN-P inhibited reverse transcriptase and infectious virus production but not p24 core antigen production. Using a microtiter XTT assay, TCN and TCN-P were active against a panel of HIV-1 and HIV-2 strains at IC50 values ranging from 0.02 to 0.46 microM. Evaluation of matched pairs of predrug and postdrug therapy HIV-1 isolates established that AZT-resistant and TIBO-resistant variants of HIV-1 were sensitive to TCN or TCN-P. Furthermore, unlike AZT and other fraudulent nucleosides, neither TCN, TCN-P, nor TCN-TP inhibited the viral reverse transcriptase. Thus, even though triciribine is a nucleoside chemically, it does not act biologically by classic nucleoside modalities but rather by a unique mechanism yet to be elucidated.
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PMID:Activity of triciribine and triciribine-5'-monophosphate against human immunodeficiency virus types 1 and 2. 768 12

In England, microbiologists at the University of Sheffield Medical School diluted herpes simplex virus-2 (HSV-2) in Eagle's Basal Medium + 5% fetal calf serum to a final concentration of 1 x 100,000 plaque-forming units/ml and HIV-1 in RPMI 1640 medium to a final concentration of 1 x 100,000 syncytium-forming units/ml. They wanted to study the inhibitory activity of the spermicidal agents nonoxynol-9, nonoxynol-11, benzalkonium chloride, menefegol, and sodium docusate. A concentration of pure nonoxynol-9 of .025% was the minimum concentration needed to inactivate HSV-2 in vitro, which was 4-160 time slower than concentrations of proprietary nonoxynol-9 preparations (2-8%) needed to have the same effect in vitro. The minimum concentration of nonoxynol-11 and benzalkonium chloride needed to inactivate HSV-2 in vitro was also .025%. Sodium docusate had a 2.5 times greater ability to inactivate HSV-2 in vitro than did nonoxynol-9 and nonoxynol-11 and benzalkonium chloride (minimum concentration = .01%). The minimum concentration of menfegol needed to inactivate HSV-2 in vitro was lower than that of the other spermicidal agents (.1%, a concentration 4 times lower than that of nonoxynol-9). All the spermicidal agents effective at inactivating HSV-2 did so in at least 30 seconds. The minimum concentration of nonoxynol-9 needed to maximally inactivate HIV-1 in vitro was .025%. it did so in 30 seconds. The lowest concentration of sodium docusate, menfegol, and benzalkonium chloride necessary for in vitro HIV-1 inactivation was also .025% (minimum time: 30 seconds for the first 2 spermicides and 2.5 minutes for the third). These findings suggest that spermicidal agents have virucidal capabilities.
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PMID:The inhibitory effect of spermicidal agents on replication of HSV-2 and HIV-1 in-vitro. 769 43

After infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. This has been observed for HIV, Hepatitis B infection in man, or after infection with lymphocytic choriomeningitis virus (LCMV) in mice. In contrast, nonneutralizing antibodies to LCMV are generated by day 7 and reach high titers by day 10. This study attempts to evaluate reasons for late and low titered neutralizing antibody responses. After a primary infection with low doses (10(2) plaque forming units) of the poorly cytopathic LCMV-WE, neutralizing antibodies were rarely produced at detectable levels before days 60 to 120. In vivo depletion of CD8+ CTL led to a marked enhancement and acceleration of kinetics of the neutralizing antibody response. In contrast, nonneutralizing antibodies, including those specific for LCMV-GP carrying the neutralizing determinant, were detectable very early, i.e., 4 to 7 days after infection, with maximum titers usually by day 10 irrespective of the presence or absence of CTL. Mice completely lacking CD8+ T cells because of deletion by homologous recombination (CD8-/-) also exhibited neutralizing antibodies early by day 10 to 20, and by day 120 reached very high titers. The neurotropic isolate LCMV-ARMSTRONG induced low but significant titers of neutralizing antibodies relatively early (i.e., by days 7 to 10), whereas the lympho-viscerotrope mutant virus LCMV-ARMSTRONG Cl-13 did not. Early and effective CTL responses causing immunopathology (and immunosuppression) correlated with the absence of neutralizing antibodies. The discrepancy between the CTL-dependent inhibition of neutralizing versus unimpaired anti-GP ELISA responses cannot be explained by different Ag doses alone. Additionally, it may reflect different kinetics of the responses, whereby the later neutralizing responses possibly requiring IgG affinity maturation may be more susceptible to general immunosuppression; also B cells expressing neutralizing receptors, but not those with antibodies binding GP (or NP), may be actively infected, therefore they present viral peptides on class I MHC Ag and may become targets for anti-LCMV-specific CTL.
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PMID:Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. 769 11


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