title: Inhibition of the alpha/beta interferon response by mouse hepatitis virus at multiple levels.
abstract: Mouse hepatitis virus (MHV) was used as a model to study the interaction of coronaviruses with the alpha/beta interferon (IFN-alpha/beta) response. While MHV strain A59 appeared to induce IFN-beta gene transcription and low levels of nuclear translocation of the IFN-beta transcription factor interferon regulatory factor 3 (IRF-3), MHV did not induce IFN-beta protein production during the course of infection in L2 mouse fibroblast cells. In addition, MHV was able to significantly decrease the level of IFN-beta 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-beta mRNA production or stability. These results indicate that MHV infection causes an inhibition of IFN-beta production at a posttranscriptional level, without altering RNA or protein stability. In contrast, MHV induced IFN-beta mRNA and protein production in the brains of infected animals, suggesting that the inhibitory mechanisms observed in vitro are not enough to prevent IFN-alpha/beta production in vivo. Furthermore, MHV replication is highly resistant to IFN-alpha/beta action, as indicated by unimpaired MHV replication in L2 cells pretreated with IFN-beta. However, when L2 cells were coinfected with MHV and NDV in the presence of IFN-beta, NDV, but not MHV, replication was inhibited. Thus, rather than disarming the antiviral activity induced by IFN-beta pretreatment completely, MHV may be inherently resistant to some aspects of the antiviral state induced by IFN-beta. These findings show that MHV employs unique strategies to circumvent the IFN-alpha/beta response at multiple steps.
authors: Department of Microbiology, University of Pennsylvania, School of Medicine, 36th Street and Hamilton Walk, Philadelphia, PA 19104-6076, USA.
authors: Jessica K
authors: JK
authors: Roth-Cross
authors: Luis
authors: L
authors: Martínez-Sobrido
authors: Erin P
authors: EP
authors: Scott
authors: Adolfo
authors: A
authors: García-Sastre
authors: Susan R
authors: SR
authors: Weiss
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology / Q000378:metabolism*; D009522:Newcastle disease virus / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D029082:Sendai virus / Q000276:immunology / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; D012333:RNA, Messenger; D016899:Interferon-beta; D046988:Proteasome Endopeptidase Complex