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Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,1 Department of Microbiology,2 Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York 100293
Received 3 January 2007/ Accepted 12 April 2007
Mouse hepatitis virus (MHV) was used as a model to study the interaction of coronaviruses with the alpha/beta interferon (IFN-
/ß) response. While MHV strain A59 appeared to induce IFN-ß gene transcription and low levels of nuclear translocation of the IFN-ß transcription factor interferon regulatory factor 3 (IRF-3), MHV did not induce IFN-ß protein production during the course of infection in L2 mouse fibroblast cells. In addition, MHV was able to significantly decrease the level of IFN-ß protein induced by both Newcastle disease virus (NDV) and Sendai virus infections, without targeting it for proteasomal degradation and without altering the nuclear translocation of IRF-3 or IFN-ß mRNA production or stability. These results indicate that MHV infection causes an inhibition of IFN-ß production at a posttranscriptional level, without altering RNA or protein stability. In contrast, MHV induced IFN-ß mRNA and protein production in the brains of infected animals, suggesting that the inhibitory mechanisms observed in vitro are not enough to prevent IFN-
/ß production in vivo. Furthermore, MHV replication is highly resistant to IFN-
/ß action, as indicated by unimpaired MHV replication in L2 cells pretreated with IFN-ß. However, when L2 cells were coinfected with MHV and NDV in the presence of IFN-ß, NDV, but not MHV, replication was inhibited. Thus, rather than disarming the antiviral activity induced by IFN-ß pretreatment completely, MHV may be inherently resistant to some aspects of the antiviral state induced by IFN-ß. These findings show that MHV employs unique strategies to circumvent the IFN-
/ß response at multiple steps.
Published ahead of print on 25 April 2007.
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