期刊
CELL HOST & MICROBE
卷 11, 期 6, 页码 607-616出版社
CELL PRESS
DOI: 10.1016/j.chom.2012.04.011
关键词
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资金
- NIH [R21-AI-080797, R56-AI-095285, RO1-NS-054695, RO1-CA044059]
- Leiden University
- Biotechnology and Biological Sciences Research Council [BB/G012067/1] Funding Source: researchfish
- BBSRC [BB/G012067/1] Funding Source: UKRI
Many viruses induce hepatitis in humans, highlighting the need to understand the underlying mechanisms of virus-induced liver pathology. The murine coronavirus, mouse hepatitis virus (MHV), causes acute hepatitis in its natural host and provides a useful model for understanding virus interaction with liver cells. The MHV accessory protein, ns2, antagonizes the type I interferon response and promotes hepatitis. We show that ns2 has 2',5'-phosphodiesterase activity, which blocks the interferon inducible 2',5'-oligoadenylate synthetase (OAS)-RNase L pathway to facilitate hepatitis development. Ns2 cleaves 2',5'-oligoadenylate, the product of OAS, to prevent activation of the cellular endoribonuclease RNase L and consequently block viral RNA degradation. An ns2 mutant virus was unable to replicate in the liver or induce hepatitis in wild-type mice, but was highly pathogenic in RNase L deficient mice. Thus, RNase L is a critical cellular factor for protection against viral infection of the liver and the resulting hepatitis.
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