Abstract |
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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Authors | Ling Zhao, Babal K Jha, Ashley Wu, Ruth Elliott, John Ziebuhr, Alexander E Gorbalenya, Robert H Silverman, Susan R Weiss |
Journal | Cell host & microbe
(Cell Host Microbe)
Vol. 11
Issue 6
Pg. 607-16
(Jun 14 2012)
ISSN: 1934-6069 [Electronic] United States |
PMID | 22704621
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Adenine Nucleotides
- Oligoribonucleotides
- RNA, Viral
- Viral Nonstructural Proteins
- Virulence Factors
- nonstructural protein, coronavirus
- 2',5'-oligoadenylate
- Interferons
- 2',5'-Oligoadenylate Synthetase
- Endoribonucleases
- 2-5A-dependent ribonuclease
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Topics |
- 2',5'-Oligoadenylate Synthetase
(antagonists & inhibitors)
- Adenine Nucleotides
(metabolism)
- Animals
- Endoribonucleases
(antagonists & inhibitors)
- Interferons
(immunology)
- Liver
(pathology, virology)
- Mice
- Murine hepatitis virus
(pathogenicity, physiology)
- Oligoribonucleotides
(metabolism)
- RNA Stability
- RNA, Viral
(metabolism)
- Viral Nonstructural Proteins
(metabolism)
- Virulence Factors
(metabolism)
- Virus Replication
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