Epigenetic Modulation of CD8⁺ T Cell Function in Lentivirus Infections: A Review

Viruses. 2018 Apr 28;10(5):227. doi: 10.3390/v10050227.

Abstract

CD8⁺ T cells are critical for controlling viremia during human immunodeficiency virus (HIV) infection. These cells produce cytolytic factors and antiviral cytokines that eliminate virally- infected cells. During the chronic phase of HIV infection, CD8⁺ T cells progressively lose their proliferative capacity and antiviral functions. These dysfunctional cells are unable to clear the productively infected and reactivated cells, representing a roadblock in HIV cure. Therefore, mechanisms to understand CD8⁺ T cell dysfunction and strategies to boost CD8⁺ T cell function need to be investigated. Using the feline immunodeficiency virus (FIV) model for lentiviral persistence, we have demonstrated that CD8⁺ T cells exhibit epigenetic changes such as DNA demethylation during the course of infection as compared to uninfected cats. We have also demonstrated that lentivirus-activated CD4⁺CD25⁺ T regulatory cells induce forkhead box P3 (Foxp3) expression in virus-specific CD8⁺ T cell targets, which binds the interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ promoters in these CD8⁺ T cells. Finally, we have reported that epigenetic modulation reduces Foxp3 binding to these promoter regions. This review compares and contrasts our current understanding of CD8⁺ T cell epigenetics and mechanisms of lymphocyte suppression during the course of lentiviral infection for two animal models, FIV and simian immunodeficiency virus (SIV).

Keywords: CD8+ T cell dysfunction; CD8+ T cells; T regulatory cells; epigenetics; feline immunodeficiency virus; human immunodeficiency virus; lentiviral infections; simian immunodeficiency virus.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cats
  • Cytokines / immunology
  • Epigenesis, Genetic*
  • HIV Infections / immunology
  • Humans
  • Immunodeficiency Virus, Feline*
  • Lentivirus Infections / immunology*
  • Lentivirus Infections / veterinary*
  • Lymphocyte Activation
  • Simian Immunodeficiency Virus*
  • T-Lymphocytes, Regulatory / immunology
  • Viremia / veterinary

Substances

  • Cytokines