ArticleJournal of virology2003
Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Functional avidity and IL-2/perforin production is linked to the emergence of mutations within HLA-B*5701-restricted epitopes and HIV-1 disease progression.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Article
- Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis.BMC bioinformatics · 2014Article
- The extent of sequence complementarity correlates with the potency of cellular miRNA-mediated restriction of HIV-1.Nucleic acids research · 2012Article
- Receptor Binding by Cholera Toxin B-Subunit and Amino Acid Modification Improves Minimal Peptide Immunogenicity.ISRN molecular biology · 2012Article
- Influence of HAART on alternative reading frame immune responses over the course of HIV-1 infection.PloS one · 2012Article
- The immune response to the RT181-189 epitope in HIV-1-infected patients is associated with viral sequence polymorphism flanking the epitope.Journal of clinical immunology · 2011Article
- CD4+ T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes.Clinical and experimental immunology · 2011Article
- Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study.Retrovirology · 2009Article
- Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985-2007.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2009Article
- Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance.Antiviral therapy · 2009Article
- Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness.PLoS pathogens · 2008Article
- Novel cytotoxic T-lymphocyte escape mutation by a three-amino-acid insertion in the human immunodeficiency virus type 1 p6Pol and p6Gag late domain associated with drug resistance.Journal of virology · 2008Article
- Antiretroviral drug therapy alters the profile of human immunodeficiency virus type 1-specific T-cell responses and shifts the immunodominant cytotoxic T-lymphocyte response from Gag to Pol.Journal of virology · 2007Article
- Immunization with HIV protease peptides linked to syngeneic erythrocytes.Infectious agents and cancer · 2007Article
- Dual selection pressure by drugs and HLA class I-restricted immune responses on human immunodeficiency virus type 1 protease.Journal of virology · 2007Article
- Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape.PloS one · 2007Article
- Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation.AIDS research and therapy · 2006Article
- Article
- Induction of T-cell immunity to antiretroviral drug-resistant human immunodeficiency virus type 1.Journal of virology · 2005Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Human immunodeficiency virus (HIV)-specific CD8(+) T-lymphocyte pressure can lead to the development of viral escape mutants, with consequent loss of immune control. Antiretroviral drugs also exert selection pressures on HIV, leading to the emergence of drug resistance mutations and increased levels of viral replication. We have determined a minimal epitope of HIV protease, amino acids 76 to 84, towards which a CD8(+) T-lymphocyte response is directed. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. Among 29 HIV-infected patients who were treated with protease inhibitors and who had developed resistance to these drugs, we show that the wild-type PR82V(76-84) epitope is commonly recognized by cytotoxic T lymphocytes (CTL) in HLA-A2-positive patients and that the CTL directed to this epitope are of high avidity. In contrast, the mutant PR82A(76-84) epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. Paradoxically, the absence of a mutation at position 82 was associated with the presence of a high-avidity CD8(+) T-cell response to the wild-type virus sequence. Our results indicate that both HIV type 1-specific CD8(+) T cells and antiretroviral drugs provide complex pressures on the same amino acid sequence of the HIV protease gene and, thus, can influence viral sequence evolution.
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