Nucleoside reverse transcriptase (RT) inhibitors of HIV block viral replication through the ability of HIV RT to incorporate chain-terminating nucleotide analogs during viral DNA synthesis. Once incorporated, the chain-terminating residue must be removed before DNA synthesis can continue. Removal can be accomplished by the excision activity of HIV RT, which catalyzes the transfer of the 3'-term...

In order to identify the basis for the relaxed enantioselectivity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and to evaluate possible cross-resistance patterns between L-nucleoside-, D-nucleosideand non-nucleoside RT inhibitors, to be utilised in anti-HIV-1 combination therapy, we applied an in vitro approach based on the utilisation of six recombinant HIV-1 RT mu...

Current consensus about treatment of HIV infection is that HAART must include two nucleoside reverse transcriptase inhibitors plus a third drug (one non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor, an integrase strand transfer inhibitor and possibly a CCR5 inhibitor). There is a lot of interest about changing the basic structure of the antiretroviral regimen so we c...

BACKGROUND The aim of this study was to characterize the mutations selected upon failure on etravirine (ETR)-containing regimen in non-nucleoside reverse transcriptase inhibitors (NNRTIs)-experienced HIV-infected patients and the associated factors. METHODS Forty-two patients displaying virological failure after a 6 months ETR-containing regimen were studied. For each patient the reverse tran...

Background The introduction of HAART has significantly prolonged the life span of HIV-infected patients. However, the error-prone nature of HIV-1 reverse transcriptase (HIV-1 RT) results in the emergence of drug-resistant viruses and threatens the effectiveness of HAART. HIV-1 RT is a primary target of two classes of drugs: nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside ...

Human immunodeficiency virus type 1 (HIV-1)-specific pyridinone reverse transcriptase (RT) inhibitors prevent HIV-1 replication in cell culture (M. E. Goldman, J. H. Nunberg, J. A. O'Brien, J.C. Quintero, W. A. Schleif, K. F. Freund, S. L. Gaul, W. S. Saari, J. S. Wai, J. M. Hoffman, P. S. Anderson, D. J. Hupe, E. A. Emini, and A. M. Stern, Proc. Natl. Acad. Sci. USA 88:6863-6867, 1991). In con...

We previously demonstrated that hybrid retrotransposons composed of the yeast Ty1 element and the reverse transcriptase (RT) of HIV-1 are active in the yeast Saccharomyces cerevisiae. The RT activity of these hybrid Ty1/HIV-1 (his3AI/AIDS RT; HART) elements can be monitored by using a simple genetic assay. HART element reverse transcription depends on both the polymerase and RNase H domains of ...

Several rare and novel NNRTI [non-nucleoside reverse transcriptase (RT) inhibitor] resistance mutations were recently detected at codons 132 and 135 in RTs from clinical isolates using the yeast-based chimaeric TyHRT (Ty1/HIV-1 RT) phenotypic assay. Ile132 and Ile135 form part of the beta7-beta8 loop of HIV-1 RT (residues 132-140). To elucidate the contribution of these residues in RT structure...

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer ...