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J. Virol. doi:10.1128/JVI.00013-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Inhibition of the IFN-/ Response by Mouse Hepatitis Virus (MHV) at Multiple Levels

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104; Department of Microbiology, and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029

^* To whom correspondence should be addressed. Email: weisssr{at}mail.med.upenn.edu.

	Abstract

Mouse hepatitis virus (MHV) was used as a model to study the interaction of coronaviruses with the IFN-/ response. While MHV strain A59 appeared to induce IFN- gene transcription and low levels of nuclear translocation of the IFN- transcription factor IRF-3, MHV did not induce IFN- protein production during the course of infection in L2 mouse fibroblast cells. In addition, MHV was able to significantly decrease the level of IFN- protein induced by both Newcastle disease virus (NDV) and Sendai virus (SeV) infections, without targeting it for proteasomal degradation and without altering the nuclear translocation of IRF-3, IFN- mRNA production or stability. These results indicate that MHV infection causes an inhibition of IFN- production at a post-transcriptional level, without altering RNA or protein stability. In contrast, MHV induced IFN- mRNA and protein production in the brains of infected animals, suggesting that the inhibitory mechanisms observed in vitro are not enough to prevent IFN-/ production in vivo. Furthermore, MHV replication is highly resistant to IFN-/ action, as indicated by unimpaired MHV replication in L2 cells pretreated with IFN-. However, when L2 cells were co-infected with MHV and NDV in the presence of IFN-, NDV, but not MHV, replication was inhibited. Thus, rather than disarming the antiviral activity induced by IFN- pretreatment completely, MHV may be inherently resistant to some aspects of the antiviral state induced by IFN-. These findings show that MHV employs unique strategies to circumvent the IFN-/ response at multiple steps.

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