Format

Send to

Choose Destination
PLoS Pathog. 2019 May 1;15(5):e1007669. doi: 10.1371/journal.ppat.1007669. eCollection 2019 May.

FOXO1 transcription factor plays a key role in T cell-HIV-1 interaction.

Author information

1
NSERM, U1016, Institut Cochin, Paris, France.
2
CNRS, UMR8104, Paris, France.
3
Université Paris Descartes, Paris, France.
4
Institut Pasteur Shangai-Chinese Academy of Sciences, Shangai, China.
5
International Associated Laboratory (LIA VirHost), CNRS, Université Paris Descartes, Institut Pasteur Paris, and Institut Pasteur Shangai-Chinese Academy of Sciences, Shangai, China.
6
CEA, Université Paris Sud, INSERM -Immunology of Viral Infections and Autoimmune Diseases department (IMVA), U1184, IDMIT Department, Fontenay-aux-Roses, France.

Abstract

HIV-1 is dependent on the host cell for providing the metabolic resources for completion of its viral replication cycle. Thus, HIV-1 replicates efficiently only in activated CD4+ T cells. Barriers preventing HIV-1 replication in resting CD4+ T cells include a block that limits reverse transcription and also the lack of activity of several inducible transcription factors, such as NF-κB and NFAT. Because FOXO1 is a master regulator of T cell functions, we studied the effect of its inhibition on T cell/HIV-1 interactions. By using AS1842856, a FOXO1 pharmacologic inhibitor, we observe that FOXO1 inhibition induces a metabolic activation of T cells with a G0/G1 transition in the absence of any stimulatory signal. One parallel outcome of this change is the inhibition of the activity of the HIV restriction factor SAMHD1 and the activation of the NFAT pathway. FOXO1 inhibition by AS1842856 makes resting T cells permissive to HIV-1 infection. In addition, we found that FOXO1 inhibition by either AS1842856 treatment or upon FOXO1 knockdown induces the reactivation of HIV-1 latent proviruses in T cells. We conclude that FOXO1 has a central role in the HIV-1/T cell interaction and that inhibiting FOXO1 with drugs such as AS1842856 may be a new therapeutic shock-and-kill strategy to eliminate the HIV-1 reservoir in human T cells.

PMID:
31042779
DOI:
10.1371/journal.ppat.1007669
Free full text

Conflict of interest statement

The authors have declared that no competing interests exist.

Supplemental Content

Full text links

Icon for Public Library of Science
Loading ...
Support Center