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Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene.

Publication ,  Journal Article
Karlsson, AC; Deeks, SG; Barbour, JD; Heiken, BD; Younger, SR; Hoh, R; Lane, M; Sällberg, M; Ortiz, GM; Demarest, JF; Liegler, T; Grant, RM ...
Published in: J Virol
June 2003

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.

Duke Scholars

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

June 2003

Volume

77

Issue

12

Start / End Page

6743 / 6752

Location

United States

Related Subject Headings

  • Virology
  • Mutation
  • Humans
  • HLA-A2 Antigen
  • HIV-1
  • HIV Protease Inhibitors
  • HIV Protease
  • HIV Infections
  • Epitopes, T-Lymphocyte
  • Drug Resistance, Viral
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Karlsson, A. C., Deeks, S. G., Barbour, J. D., Heiken, B. D., Younger, S. R., Hoh, R., … Nixon, D. F. (2003). Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. J Virol, 77(12), 6743–6752. https://doi.org/10.1128/jvi.77.12.6743-6752.2003
Karlsson, Annika C., Steven G. Deeks, Jason D. Barbour, Brandon D. Heiken, Sophie R. Younger, Rebecca Hoh, Meghan Lane, et al. “Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene.J Virol 77, no. 12 (June 2003): 6743–52. https://doi.org/10.1128/jvi.77.12.6743-6752.2003.
Karlsson AC, Deeks SG, Barbour JD, Heiken BD, Younger SR, Hoh R, et al. Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. J Virol. 2003 Jun;77(12):6743–52.
Karlsson, Annika C., et al. “Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene.J Virol, vol. 77, no. 12, June 2003, pp. 6743–52. Pubmed, doi:10.1128/jvi.77.12.6743-6752.2003.
Karlsson AC, Deeks SG, Barbour JD, Heiken BD, Younger SR, Hoh R, Lane M, Sällberg M, Ortiz GM, Demarest JF, Liegler T, Grant RM, Martin JN, Nixon DF. Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. J Virol. 2003 Jun;77(12):6743–6752.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

June 2003

Volume

77

Issue

12

Start / End Page

6743 / 6752

Location

United States

Related Subject Headings

  • Virology
  • Mutation
  • Humans
  • HLA-A2 Antigen
  • HIV-1
  • HIV Protease Inhibitors
  • HIV Protease
  • HIV Infections
  • Epitopes, T-Lymphocyte
  • Drug Resistance, Viral