The membrane-bound transcription factor CREB3L1 is activated in response to virus infection to inhibit proliferation of virus-infected cells

Bray Denard, Joachim Seemann, Qiuyue Chen, Austin Gay, Hua Huang, Yan Chen, Jin Ye

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

CREB3L1/OASIS is a cellular transcription factor synthesized as a membrane-bound precursor and activated by regulated intramembrane proteolysis in response to stimuli like ER stress. Comparing gene expression between Huh7 subclones that are permissive for hepatitis C virus (HCV) replication versus the nonpermissive parental Huh7 cells, we identified CREB3L1 as a host factor that inhibits proliferation of virus-infected cells. Upon infection with diverse DNA and RNA viruses, including murine γ-herpesvirus 68, HCV, West Nile virus (WNV), and Sendai virus, CREB3L1 was proteolytically cleaved, allowing its NH 2 terminus to enter the nucleus and induce multiple genes encoding inhibitors of the cell cycle to block cell proliferation. Consistent with this, we observed a necessity for CREB3L1 expression to be silenced in proliferating cells that harbor replicons of HCV or WNV. Our results indicate that CREB3L1 may play an important role in limiting virus spread by inhibiting proliferation of virus-infected cells.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalCell Host and Microbe
Volume10
Issue number1
DOIs
StatePublished - Jul 21 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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