ArticleJournal of virology2001
Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.
Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 84 citations in OpenAlex.
- Human immunodeficiency virus type 1 fitness is a determining factor in viral rebound and set point in chronic infection.Journal of virology · 2003Trial
- Consensus Sequences forViruses · 2025Article
- Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms.Nature reviews. Genetics · 2015Review
- Interplay between single resistance-associated mutations in the HIV-1 protease and viral infectivity, protease activity, and inhibitor sensitivity.Antimicrobial agents and chemotherapy · 2012Article
- Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants.Viral immunology · 2012Article
- Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process.Molecular biology international · 2012Article
- Molecular Basis for Drug Resistance in HIV-1 Protease.Viruses · 2010Article
- Role of Gag in HIV Resistance to Protease Inhibitors.Viruses · 2010Article
- Phenotypic and genotypic characterization of human immunodeficiency virus type 1 CRF07_BC strains circulating in the Xinjiang Province of China.Retrovirology · 2009Article
- Clinical significance of human immunodeficiency virus type 1 replication fitness.Clinical microbiology reviews · 2007Review
- HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions.Journal of molecular biology · 2007Article
- Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region.Journal of virology · 2007Article
- Adaptation of HIV-1 depends on the host-cell environment.PloS one · 2007Article
- Evolution of human immunodeficiency virus type 1 protease genotypes and phenotypes in vivo under selective pressure of the protease inhibitor ritonavir.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
- Colinearity of reverse transcriptase inhibitor resistance mutations detected by population-based sequencing.Journal of acquired immune deficiency syndromes (1999) · 2003Article
- A naturally occurring substitution in human immunodeficiency virus Tat increases expression of the viral genome.Journal of virology · 2003Article
- Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection.Journal of virology · 2003Article
- Isolation and molecular characterization of a nelfinavir (NFV)-resistant human immunodeficiency virus type 1 that exhibits NFV-dependent enhancement of replication.Journal of virology · 2003Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.
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