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Viruses 2018, 10(5), 227; https://doi.org/10.3390/v10050227

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

1
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
2
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Received: 22 March 2018 / Revised: 23 April 2018 / Accepted: 24 April 2018 / Published: 28 April 2018
(This article belongs to the Special Issue Nonprimate Lentivirus)
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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). View Full-Text
Keywords: CD8+ T cells; T regulatory cells; CD8+ T cell dysfunction; epigenetics; lentiviral infections; feline immunodeficiency virus; simian immunodeficiency virus; human immunodeficiency virus CD8+ T cells; T regulatory cells; CD8+ T cell dysfunction; epigenetics; lentiviral infections; feline immunodeficiency virus; simian immunodeficiency virus; human immunodeficiency virus
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Nag, M.; De Paris, K.; E. Fogle, J. Epigenetic Modulation of CD8+ T Cell Function in Lentivirus Infections: A Review. Viruses 2018, 10, 227.

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