Journal article

Publication year: 2012

Pages: 607-616

Journal: Cell Host & Microbe

Volume number: 11

Issue number: 6

ISSN: 1931-3128

eISSN: 1934-6069

Open access status: Green

DOI Link: https://doi.org/10.1016/j.chom.2012.04.011

Publisher: Cell Press

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.

Harvard Citation style: Zhao, L., Jha, B., Wu, A., Elliott, R., Ziebuhr, J., Gorbalenya, A., et al. (2012) Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology, Cell Host & Microbe, 11(6), pp. 607-616. https://doi.org/10.1016/j.chom.2012.04.011

APA Citation style: Zhao, L., Jha, B., Wu, A., Elliott, R., Ziebuhr, J., Gorbalenya, A., Silverman, R., & Weiss, S. (2012). Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology. Cell Host & Microbe. 11(6), 607-616. https://doi.org/10.1016/j.chom.2012.04.011