Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human colonic adenocarcinoma cell line HT29 can be infected with various isolates of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). In some cases, the virus was able to perform its complete cycle of replication as demonstrated by the persistent production of mature viral particles in the cell-free culture supernatant. We have cultured HT29 cells chronically infected with the replicative strain HIV1-NDK in a chemically defined serum-free medium. Under these conditions, the cells were able to maintain a high level of viral replication, as demonstrated by reverse transcriptase activities and in situ hybridization studies. By indirect immunofluorescence labeling and electron microscopy, we observed that serum starvation was associated with the differentiation of HIV-1-infected HT29 cells into mucous-secreting cells resembling epithelial goblet cells of the colonic mucosa. These mucous-secreting cells, which accounted for 50% of the overall population, produced mature particles of HIV through their apical membrane in the vicinity of mucous granules. These data suggest that HIV-infected goblet cells in the colonic mucosa may produce the virus in the colorectal lumen; this could explain the route of transmission of HIV in the case of anal intercourse.
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PMID:Replication and apical budding of HIV-1 in mucous-secreting colonic epithelial cells. 128 Jun 83

Human T-lymphoblastoid cells H9, CEM and CEM-clone 5 were selected for growth in RPMI 1640 supplemented with transferrin 5 micrograms/ml, insulin 5 micrograms/ml and sodium selenite 5 ng/ml. After 40 days of adaptation to serum-free medium, these cells displayed growth, morphology, and expression of CD4 similar to serum-supplemented cultures. Infection of these cells with two strains of HIV-1 (LAV and NDK) and a strain of HIV-2 (ROD) was as efficient in serum-free as in serum-supplemented medium as demonstrated by reverse transcriptase activity in the culture supernatants of infected cells. Furthermore, HIV-induced cytopathogenicity was observed in serum-free cultures, demonstrating that both HIV infection and cytopathic effect did not require the presence of serum components. Electron microscopy showed that mature viral particles were produced from infected cells cultured in serum-free medium. Finally, the ability of monoclonal antibody OKT4 A to inhibit infection by HIV-1 LAV but not by HIV-1 NDK was the same with and without serum in the culture medium, demonstrating that both CD4-dependent and CD4-independent infections can occur in the total absence of serum. Human T-lymphoblastoid cells adapted for growth in serum-free medium provide therefore a complementary tool for the study of HIV infection and cytopathogenicity under defined conditions.
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PMID:Human T-lymphoblastoid cells selected for growth in serum-free medium provide new tools for study of HIV replication and cytopathogenicity. 172 73

In vitro evaluation of a large chemical library of pharmacologically acceptable prototype compounds in a high-capacity, cellular-based screening system has led to the discovery of another family of human immunodeficiency virus type 1 (HIV-1) inhibitors. Through optimization of a lead compound, several alpha-anilinophenylacetamide (alpha-APA) derivatives have been identified that inhibit the replication of several HIV-1 strains (IIIB/LAI, RF, NDK, MN, HE) in a variety of host cell types at concentrations that are 10,000- to 100,000-fold lower than their cytotoxic concentrations. The IC50 of the alpha-APA derivative R 89439 for HIV-1 cytopathicity in MT-4 cells was 13 nM. The median 90% inhibitory concentration (IC90) in a variety of host cells was 50-100 nM. Although these alpha-APA derivatives are active against a tetrahydroimidazo [4,5,1-jk][1,4]benzodiazepin-2(1H)-thione-(TIBO)-resistant HIV-1 strain, they do not inhibit replication of HIV-2 (strains ROD and EHO) or simian immunodeficiency virus (strains Mac251, mndGB1, and agm3). An HIV-1 strain containing the Tyr181-->Cys mutation in the reverse transcriptase region displayed reduced sensitivity. alpha-APA derivative R 89439 inhibited virion and recombinant reverse transcriptase of HIV-1 but did not inhibit that of HIV-2. Reverse transcriptase inhibition depended upon the template/primer used. The relatively uncomplicated synthesis of R 89439, its potent anti-HIV-1 activity, and its favorable pharmacokinetic profile make R 89439 a good candidate for clinical studies.
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PMID:Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase. 768 Apr 76

Inhibition of HIV-1 replication by differently substituted spirocyclopropyl compounds has been evaluated. Compound 21 showed a moderate activity (EC50 ranging from 2.3 to 5.8 micrograms/ml) against different HIV-1 strains (IIIB, RF, NDK, and an AZT-resistant strain) in different cell lines (MT-4 and C-8166 cells), while it was cytotoxic at 77.7 micrograms/ml, resulting in a selectivity index of 34. This compound was inactive against HIV-2 (ROD) and SIV (MAC251). From "time-of-addition" experiments compound 21, like AZT, appeared to inhibit HIV-1 at the reverse transcriptase step.
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PMID:Inhibition of human immunodeficiency virus type (HIV-1) replication by some diversely functionalized spirocyclopropyl derivatives. 1036 1

The anti-HIV activity of a novel series of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs) has been described. The compounds were synthesized via Curtius rearrangement of appropriate sulfamoylcarboxy azides which, in turn, were prepared from known starting materials. Several 4-substituted-2-benzyl-derivatives were found to selectively inhibit human immunodeficiency virus type 1 [HIV-1 (IIIB)] replication in MT-4 and CEM cells. These TTDs were also effective against other strains of HIV-1 (RF, HE, MN, NDK), including those that are resistant to AZT, but not against HIV-2 (ROD) or simian immunodeficiency virus [SIV(MAC251)] at subtoxic concentrations. Some of the test compounds exhibited antiviral activity against L100I RT mutant virus, but significantly lost antiviral activity against K103N, V106A, E138K, Y181C and Y188H RT mutant viruses. Compounds 6d, 6f and 6g were inhibitory to HIV-1 RT at concentrations that rank between 16.4 and 59.8 microM (nevirapine: IC50 = 4.5 microM against HIV-1 RT). Inhibition of HIV-1 RT by compound 6g was purely non-competitive with respect to the natural substrate (dGTP), which is in agreement with the nature of inhibition shown by other NNRTIs such as nevirapine and delarvidine. A structure-activity relationship was established for the anti-HIV activity of these heterocyclic compounds. TTDs represent a new chemical class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).
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PMID:Synthesis and anti-HIV activity of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs): a new family of HIV-1 specific non-nucleoside reverse transcriptase inhibitors. 1065 85