T cells target APOBEC3 proteins in human immunodeficiency virus type 1-infected humans and simian immunodeficiency virus-infected Indian rhesus macaques

J Virol. 2013 Jun;87(11):6073-80. doi: 10.1128/JVI.00579-12. Epub 2013 Mar 27.

Abstract

APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • Adult
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology*
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / immunology*
  • Cytosine Deaminase / genetics
  • Cytosine Deaminase / immunology*
  • Female
  • Gene Products, vif / genetics
  • Gene Products, vif / immunology
  • HIV Infections / enzymology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Humans
  • Macaca mulatta
  • Male
  • Simian Acquired Immunodeficiency Syndrome / enzymology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / physiology*

Substances

  • Gene Products, vif
  • APOBEC3F protein, human
  • Cytosine Deaminase
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase