Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A lambda phage expression methodology was adapted to dissect protein/ligand interactions efficiently through the creation and rapid screening of large numbers of mutants. Here we describe the method and its specific application to the interaction between the external envelope glycoprotein of the human immunodeficiency virus (HIV-1), gp120, and the human cell surface protein CD4. Random substitutions were introduced throughout the gp120 binding region (amino acids 38-62) in the amino-terminal domain of CD4 by oligonucleotide mutagenesis. These mutations were expressed within phage plaques and directly screened for their effect on binding of gp120 using a modified phage plaque lift procedure. Plaques showing increased, decreased, and no effect on binding were identified and mutations were verified by sequence analysis. In this manner, 25 unique mutations were identified that altered CD4 binding to gp120. A new site was identified at which mutations reduced binding to gp120 and several novel amino acid substitutions were defined at sites previously implicated in binding. Of particular interest, this in vitro genetic approach identified a mutation which significantly increased binding to gp120. The phenotypes of several of these mutants were further characterized by quantitative measurement of their binding affinity. The results confirmed the accuracy of the phenotypic selection and demonstrated that the sensitivity of the system allowed detection of a 3-4-fold increase or decrease in affinity. In the context of the recently determined atomic structure of CD4, these results further implicate residues in the CDR2-like region and in an adjacent loop in recognition of gp120. This methodology should be generally applicable to other high affinity protein/ligand interactions that are compatible with expression in Escherichia coli.
 ...
PMID:An efficient phage plaque screen for the random mutational analysis of the interaction of HIV-1 gp120 with human CD4. 153 31

Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infection in nanomolar-micromolar concentrations, but no anti-HIV effect was found with the lectin HPA, mainly reacting with O-linked oligosaccharides. HSV-1 infectivity was measured in a plaque reduction assay using Vero cells, and while both N- and O-linked oligosaccharide -specific lectins inhibited HSV-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses.
 ...
PMID:Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins. 165 37

Visible plaque index (VPI), gingival bleeding index (GBI) and pocket depth (PD) were analyzed in relation to potential periodontal pathogenic microorganisms and peripheral numbers of T4+ and T8+ lymphocyte subsets in 10 patients with human immunodeficiency virus (HIV) infection, 10 patients with AIDS related complex (ARC) and 10 patients with acquired immune deficiency syndrome (AIDS). 10 healthy persons served as controls. Periodontal disease in patients with more advanced stages of HIV infection were related to the severity of the systemic disease, and to decreasing numbers of T4+ lymphocytes in peripheral blood, but not to VPI or the occurrence of periodontal pathogenic micro-organisms.
 ...
PMID:Periodontal disease in HIV-infected patients in relation to lymphocyte subsets and specific micro-organisms. 167 65

HIV-2 infection of eight rhesus macaques and two baboons was studied. Most animals were preselected for HIV-2 inoculation by testing their peripheral blood mononuclear cells (PBMC) for susceptibility to virus isolates from the Ivory Coast. The virus strains used (HIV-2UC2, HIV-2UC3, and HIV-2UC7) were also chosen by in vitro screening in PBMC for high replicating ability and cytopathicity. All the animals seroconverted within 2-4 weeks of infection and remained seropositive throughout the duration of the study. One macaque was sacrificed after 2 years, suffering from diarrhea and weight loss, and one baboon died of non-HIV-related causes. The remaining animals are asymptomatic, with normal CD4/CD8 ratios. Virus has been recovered from most animals, and persistent HIV-2 replication has been noted in three macaques and a baboon. Host range studies in T, B, and monocyte cell lines showed little or no differences between isolates obtained after inoculation and the original virus inoculum. However, isolates from the macaque that showed clinical symptoms were more cytopathic as reflected by plaque formation in MT-4 cells. The HIV-2-infected macaque or baboon could be useful as an animal model for elucidating the mechanisms of HIV pathogenesis and for evaluating potential antiviral therapies and vaccines.
 ...
PMID:Persistent infection of baboons and rhesus monkeys with different strains of HIV-2. 167 64

A new class of membrane-active ether lipid (EL) analogs of platelet-activating factor were studied for in vitro anti-HIV-1 activity. Human T-cell (CEM-ss) monolayers or suspension cultures were used to determine effects of structural modifications of Type A phosphorus-containing and Type B nonphosphorus EL analogs on (a) the inhibitory concentration50 (IC50) for HIV-1 syncytial plaque formation and cell growth, and, (b) virus budding at the cell plasma membrane. Results indicate that representative Type A and Type B EL inhibit HIV-1 but not herpes simplex virus type 2 plaque formation when added before or up to 2 days after viral infection. Anti-HIV-1 activity does not involve direct inactivation of virus infectivity. Type A EL (IC50 range = 0.2-1.4 microM) with alkyoxy, alkylthio, or alkyamido substitution at glycerol position 1 and ethoxy or methoxy substitution at position 2, and Type B compounds (IC50 range = 0.33-0.63 microM) with an inverse choline or nitrogen heterocyclic substitution at position 3 have selective activity against HIV-1-infected T-cells. EL treatment of HIV-1-infected cells is associated with subsequent release of reverse transcriptase activity, but infectious virus production is inhibited with time after infection. Electron microscopic examination of HIV-1-infected and EL-treated cells revealed absence of detectable budding virus at the plasma membrane but presence of intracytoplasmic vacuolar virus particles. In summary, these data suggest that EL analogs are a novel class of agents that induce defective intracytoplasmic vacuolar HIV-1 formation in T-cells. Being membrane interactive, EL are ideally suited for combination chemotherapy with DNA-interactive anti-HIV nucleoside analogs.
 ...
PMID:Novel membrane-interactive ether lipid analogs that inhibit infectious HIV-1 production and induce defective virus formation. 169 29

Antigenic mutants of HIV-1 were isolated from three plaque-cloned viruses by the resistance of the virus to neutralizing mAb 0.5 beta against V3 domain of viral gp120, when the viruses were passaged in the presence of the antibody. However, when chronically infected MOLT-4 cells were treated with 0.5 beta mAb, recovered viruses from the 0.5 beta-treated cells showed no antigenic changes. The extent of genomic variation among antigenically distinct isolates was examined by nucleotide sequencing, which revealed a few base substitutions in 0.5 beta-binding site of all mutants isolated. The predicted amino acid replacements within 0.5 beta reacting epitope (V3 domain) causing the altered antigenicity were also identified for each of three isolates. Particularly, in one of the mutants, the most conserved Gly-Pro-Gly-Arg region located at the center of the V3 domain was changed to Gly-Gln-Gly-Arg. The radioimmunoprecipitation and synthetic peptide analyses revealed that this Pro320----Gln substitution reduced the binding affinity with 0.5 beta, although other mutations observed in the other mutants did not affect the binding affinity in radioimmunoprecipitation. We also observed that nucleic acid substitutions in the V3 domain occurred frequently in the absence of 0.5 beta mAb during our in vitro acute infection system using MT-4 cells.
 ...
PMID:Generation of neutralization-resistant HIV-1 in vitro due to amino acid interchanges of third hypervariable env region. 170 2

A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. The lead compound, BI-RG-587, had a 50% inhibitory concentration of 84 nM against HIV-1 reverse transcriptase activity. This compound reduced plaque formation of HIV-1 in HeLa cells expressing the CD4 receptor by 50% at 15 nM. BI-RG-587 at comparable concentrations inhibited the production of p24 antigen following the acute infection of CEM T-lymphoblastoid cells or primary human monocyte-derived macrophages with HIV-1. No inhibitory effects against HIV-2 or against three picornaviruses were detected. Zidovudine (3'-azido-3'-deoxythymidine [AZT])-susceptible and AZT-resistant isolates of HIV-1 were equally susceptible to BI-RG-587. AZT and BI-RG-587 exhibited synergistic inhibition of HIV-1BRU at all concentrations examined.
 ...
PMID:BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. 170 76

Alpha-lipoic acid, a naturally occurring disulfide-compound that acts as a cellular coenzyme, inhibits replication of HIV-1 in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with HTLV IIIB and HIV-1 Wal (a wild type HIV-1 isolate). We observed a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic effect) formation, reverse transcriptase activity and plaque formation on CD4-transformed HeLa-cells. An over 90% reduction of reverse transcriptase activity could be achieved with 70 micrograms alpha-lipoic acid/ml, a complete reduction of plaque-forming units at concentrations of greater than or equal to 35 micrograms alpha-lipoic acid/ml. An augmentation of the antiviral activity was seen by combination of zidovudine and low dose of alpha-lipoic acid (7 micrograms/ml). Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mono-nuclear cells and T-cell lines even in concentrations of greater than or equal to 70 micrograms/ml. Therefore, we propose the inclusion of alpha-lipoic acid into chemotherapy trials in combination with zidovudine.
 ...
PMID:Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. 172 77

The purpose of this study was to evaluate the association of periodontal health and human immunodeficiency virus infection among individuals in the early stages of disease who were participating in randomized placebo-controlled clinical trials of zidovudine. Previous reports have described a rapidly progressive periodontitis and atypical gigivitis associated with late stages of infection by the human immunodeficiency virus. A health history was completed by each subject. Baseline oral examinations were completed on 97 asymptomatic patients and nine with AIDS-related complex (ARC) during their regular clinic visit. Follow-up examinations were conducted at 3-month intervals throughout the 48 weeks of the oral study. Evaluations of plaque, calculus, gingival abnormalities, caries, and periodontal disease were conducted. Periodontal measurements included plaque index (PI), gingival index (GI), bleeding index (BI), probing depth (PD), and observation for cratering, necrosis, and tooth mobility on six teeth in each patient. More than half of the subjects had visited their dentist during the previous year and had had an oral prophylaxis; less than 25% of them had had either restorative work or extractions. The mean scores for periodontal indices averaged over the course of the study in asymptomatic and ARC respectively were: PI: 0.9 (SE 0.04) and 0.9 (SE 0.08), 0.818; GI: 1.0 (SE 0.04) and 0.9 (SE 0.07), P = 0.412; BI: 0.6 (SE 0.04) and 0.4 (SE 0.07), P = 0.278; PD: 2.9 (SE 0.05) and 2.6 (SE 0.10), P = 0.140. There was no evidence of cratering, necrosis, or tooth mobility in either group. Few had calculus or dental caries. There were no clinically significant differences detected between ARC versus asymptomatic patients. Dental histories and oral examinations showed that two groups of patients in early stages of HIV-disease were in good periodontal health.
 ...
PMID:Periodontal status of individuals in early stages of human immunodeficiency virus infection. 174 94

Few reported studies have evaluated the periodontal status of individuals infected by human immunodeficiency virus (HIV). The majority of these reports have evaluated the periodontal status of individuals presenting to dental care facilities due to oral problems. These reports suggest that severe gingival inflammation and attachment loss are often associated with HIV seropositive patients. The purpose of this study was to evaluate the periodontal status of HIV seropositive patients without biasing the data towards those presenting to dentists with oral problems. Sixty-three consenting male patients presenting to the infectious disease clinic at the Medical College of Virginia Hospitals were examined to determine the status of their periodontal health. Gingival index, plaque index, pocket depths, and attachment loss were determined using standard indices. Participants were first grouped according to the modified CDC Classification System for HIV infection and then categorized according to HIV risk factors for purposes of statistical analysis. No significant differences could be found in the gingival or periodontal status of subjects who were HIV seropositive versus those with AIDS. Periodontal status was also not significantly different for individuals based upon risk group. Periodontal health of the participants was similar to the general population (HIV status unknown). This would indicate that, although HIV gingivitis and HIV periodontitis have been documented in a number of HIV-infected patients, the frequency of affected individuals is less than previous reports would suggest.
 ...
PMID:Periodontal status of HIV-seropositive and AIDS patients. 177 Apr 22


1 2 3 4 5 6 7 8 9 10 Next >>