ArticleJournal of virology1996
Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication.
Article in Journal of virology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 91 citations in OpenAlex.
- FRET-based assay to screen inhibitors of HIV-1 reverse transcriptase and nucleocapsid protein.Nucleic acids research · 2016Article
- Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness.The Journal of general virology · 2013Article
- Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase.Journal of virology · 2012Article
- In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor.Antimicrobial agents and chemotherapy · 2011Article
- Comparative biochemical analysis of recombinant reverse transcriptase enzymes of HIV-1 subtype B and subtype C.Retrovirology · 2010Article
- The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity.Antimicrobial agents and chemotherapy · 2010Article
- Clinical significance of human immunodeficiency virus type 1 replication fitness.Clinical microbiology reviews · 2007Review
- Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages.Journal of virology · 2007Article
- Increased multinucleoside drug resistance and decreased replicative capacity of a human immunodeficiency virus type 1 variant with an 8-amino-Acid insert in the reverse transcriptase.Journal of virology · 2005Article
- Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues.Journal of virology · 2005Article
- Role of minority populations of human immunodeficiency virus type 1 in the evolution of viral resistance to protease inhibitors.Journal of virology · 2004Article
- Multiple effects of the M184V resistance mutation in the reverse transcriptase of human immunodeficiency virus type 1.Clinical and diagnostic laboratory immunology · 2003Review
- Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection.Journal of virology · 2003Article
- The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1.Journal of virology · 2002Article
- Genotypic testing for human immunodeficiency virus type 1 drug resistance.Clinical microbiology reviews · 2002Review
- A fossil record of zidovudine resistance in transmitted isolates of HIV-1.Proceedings of the National Academy of Sciences of the United States of America · 2001Review
- Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.Journal of virology · 2001Article
- A Guide to HIV-1 Reverse Transcriptase and Protease Sequencing for Drug Resistance Studies.HIV sequence compendium · 2001Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Certain amino acid substitutions in the reverse transcriptase (RT), including D67N, K70R, T215Y, and K219Q, cause high-level resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (3'-azidothymidine; AZT) and appear to approximate the template strand of the enzyme-template-primer complex in structural models. We studied whether this set of mutations altered RT-template-primer interaction as well as their effect on virus replication in the absence of inhibitor. When in vitro polymerization was limited to a single association of an RT with an oligodeoxynucleotide-primed heteropolymeric RNA template (a single processive cycle), recombinant-expressed mutant 67/70/215/219 RT synthesized 5- to 10-fold more high-molecular-weight DNA products (>200 nucleotides in length) than wild-type RT. This advantage was maintained as deoxynucleoside triphosphate (dNTP) concentrations were decreased to limiting levels. In contrast, no difference was seen between wild-type and mutant RTs under conditions allowing repeated associations of enzyme with template-primer. Because intracellular dNTP concentrations are low prior to mitogenic stimulation, we compared replication of mutant 67/70/215/219 virus and wild-type virus in peripheral blood mononuclear cells (PBMC) stimulated before and after infection. In the absence of inhibitor, mutant 67/70/215/219 virus had a replication advantage in PBMC stimulated with phytohemagglutinin and interleukin-2 after infection, but virus replication was similar in PBMC stimulated before infection in vitro. The results confirm that RT mutations D67N, K70R, T215Y, and K219Q affect an enzyme-template-primer interaction in vitro and suggest that such substitutions may affect HIV-1 pathogenesis during therapy by increasing viral replication capacity in cells stimulated after infection.
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