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

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).

Epigenetic mediated functional reprogramming of immune cells leads to HBsAg seroconversion in Hepatitis B Virus Reactivation patients

“…[10] Epigenetic modulation reduces the FOXP3 binding to interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ promoters in lentivirus-specific CD8 + T cells. [11] At the same time, with epigenetic modulation, reduced expression of co-stimulatory molecules like CD40, CD80, CD86 and secretion of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6 and IL-12 inhibits the activation of Th1 and Th17 responses and granzyme B producing CD8 + T cells. [12,13] However, recently epigenomic and transcriptomic regulome revealed that HBVspecific CD8+ T cells which are not terminally exhausted showed long-term memory and polyfunctionality in chronically HBV-infected HCC patients.…”

Er3+/Yb3+ co-doped nanocrystals modified with 6-aminocaproic acid for temperature sensing in biomedicine

“…They are highly infectious and extremely harmful, particularly lentiviruses such as human immunodeficiency virus, and the medical community has not yet found an efficient and reasonable treatment strategy. 13 Recently, researchers have found that lentiviral nucleocapsids play a crucial role in the lentiviral replication cycle and are considered ideal targets for antiviral therapy. 14 Detecting the temperature changes that accompany nucleocapsid binding and exploring the effects of temperature changes on the activity of proteases and reverse transcriptases, helps to deepen the understanding of lentiviral replication and develop more efficient and rational lentiviral treatment strategies.…”