ZIKV induction of tristetraprolin in endothelial and Sertoli cells post-transcriptionally inhibits IFNβ/λ expression and promotes ZIKV persistence.

ABSTRACT:

Importance

Our findings define a novel role for ZIKV-induced TTP expression in regulating IFNβ/IFNλ production in primary hBMECs and Sertoli cells. These cells comprise key physiological barriers subverted by ZIKV to access brain and testicular compartments and serve as reservoirs for persistent replication and dissemination. We demonstrate for the first time that the ARE-binding protein TTP is virally induced and post-transcriptionally regulates IFNβ/IFNλ secretion. In ZIKV-infected hBMEC and Sertoli cells, TTP knockout increased IFNβ/IFNλ secretion, while TTP expression blocked IFNβ/IFNλ secretion. The TTP-directed blockade of IFN secretion permits ZIKV spread and persistence in hBMECs and Sertoli cells and may similarly augment ZIKV spread across IFNλ-protected placental barrier

SUBMITTER: Schutt WR 

PROVIDER: S-EPMC10653947 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature