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Viruses. 2018 Apr 28;10(5). pii: E227. doi: 10.3390/v10050227.

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

Author information

1
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. mnag@ncsu.edu.
2
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. kristina_abel@med.unc.edu.
3
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA. jefogle@ncsu.edu.

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

PMID:
29710792
PMCID:
PMC5977220
DOI:
10.3390/v10050227
[Indexed for MEDLINE]
Free PMC Article

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