P53-derived host restriction of HIV-1 replication by protein kinase R-mediated Tat phosphorylation and inactivation.

ABSTRACT:

Unlabelled

Tumor suppressor p53 has been suggested to be a host restriction factor against HIV-1 replication, but the detailed molecular mechanism has remained elusive for decades. Here, we demonstrate that p53-mediated HIV-1 suppression is attributed to double-stranded RNA (dsRNA)-dependent protein kinase (PKR)-mediated HIV-1 trans-activator (Tat) phosphorylation and inactivation. p53 silencing significantly enhanced HIV-1 replication in infected cells. Ectopic expression of p53 suppressed Tat activity, which was rescued by PKR silencing. In addition, ectopic expression of PKR abolished Tat activity in p53(-/-) and eIF2α(CA) cells. Finally, we found that HIV-1 infection activates p53, followed by the induction and activation of PKR. PKR directly interacted with HIV-1 Tat and phosp

SUBMITTER: Yoon CH 

PROVIDER: S-EPMC4442402 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature