Inhibition of TRF2 accelerates telomere attrition and DNA damage in naive CD4 T cells during HCV infection.

ABSTRACT: T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat bi

SUBMITTER: Nguyen LN 

PROVIDER: S-EPMC6125360 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature