TY - JOUR
T1 - The membrane-bound transcription factor CREB3L1 is activated in response to virus infection to inhibit proliferation of virus-infected cells
AU - Denard, Bray
AU - Seemann, Joachim
AU - Chen, Qiuyue
AU - Gay, Austin
AU - Huang, Hua
AU - Chen, Yan
AU - Ye, Jin
N1 - Funding Information:
We thank Michael S. Brown and Joseph L. Goldstein for their support and advice; Michael Gale for his gifts of Huh7-K2040, and Huh7-WNV2 cells; Charlie Rice, Guangxiang Luo, and Pinghui Feng for their gifts of Huh7.5 cells, Huh7-GL cells, and MHV-68, respectively; Takaji Wakita for the JFH technology; Lisa Beatty, Angela Carroll, Shomanike Head, and Ijeoma Onwuneme for help with tissue culture; and Saada Abdalla for technical assistance. This work was supported by grants from the National Institutes of Health (AI 090119) and Perot Family Foundation.
PY - 2011/7/21
Y1 - 2011/7/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2011.06.006
DO - 10.1016/j.chom.2011.06.006
M3 - Article
C2 - 21767813
AN - SCOPUS:79960546549
SN - 1931-3128
VL - 10
SP - 65
EP - 74
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -