USP18 is a significant driver of memory CD4 T-cell reduced viability caused by type I IFN signaling during primary HIV-1 infection.

ABSTRACT: The loss of Memory CD4 T-cells (Mem) is a major hallmark of HIV-1 immuno-pathogenesis and occurs early during the first months of primary infection. A lot of effort has been put into understanding the molecular mechanisms behind this loss, yet they still have not been fully identified. In this study, we unveil the unreported role of USP18 in the deleterious effects of sustained type I IFN signaling on Mem, including HIV-1-specific CD4 T-cells. We find that interfering with IFN-I signaling pathway in infected patients, notably by targeting the interferon-stimulated gene USP18, resulted in reduced PTEN expression similar to those observed in uninfected control donors. We show that AKT activation in response to cytokine treatment, T-cell receptor (TcR) triggering, as well as HIV-1 Gag stimula

SUBMITTER: Dagenais-Lussier X 

PROVIDER: S-EPMC6837632 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature