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PMID: 17459917 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Inhibition of the alpha/beta interferon response by mouse hepatitis virus at multiple levels.

Journal of virology ·Vol. 81 ·No. 13 ·2007-07-00 ·Pages 7189-99

Roth-Cross JK, Martínez-Sobrido L, Scott EP, García-Sastre A, Weiss SR

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.

MeSH Terms
Active Transport, Cell Nucleus/immunology Animals Antiviral Agents/immunology,metabolism,pharmacology Cell Nucleus/immunology,metabolism Chlorocebus aethiops Fibroblasts/immunology,metabolism,virology Hepatitis, Viral, Animal/immunology,metabolism Interferon Regulatory Factor-3/immunology,metabolism Interferon-alpha/immunology,metabolism Interferon-beta/immunology,metabolism,pharmacology Male Mice Murine hepatitis virus/immunology,metabolism Newcastle disease virus/immunology,metabolism Proteasome Endopeptidase Complex/immunology,metabolism RNA Stability/immunology RNA, Messenger/biosynthesis,immunology Sendai virus/immunology,metabolism Vero Cells Virus Replication/immunology
Chemicals
Antiviral Agents Interferon Regulatory Factor-3 Interferon-alpha Irf3 protein, mouse RNA, Messenger Interferon-beta Proteasome Endopeptidase Complex
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Roth-Cross Jessica K
Department of Microbiology, University of Pennsylvania, School of Medicine, 36th Street and Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Martínez-Sobrido Luis
Scott Erin P
García-Sastre Adolfo
Weiss Susan R
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.00013-07
Published
2007-07-00
Epub
2007-00-25
Pages
7189-99
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1933268
Subset
IM
Grants
NIAID NIH HHS · AI-52106 · United States
NINDS NIH HHS · T32 NS007180 · United States
NIAID NIH HHS · P01 AI052106 · United States
NIAID NIH HHS · AI-60021 · United States
NINDS NIH HHS · NS-54695 · United States
NIAID NIH HHS · U19 AI-62623 · United States
NIAID NIH HHS · U19 AI062623 · United States
NIAID NIH HHS · N01AI60021 · United States
NINDS NIH HHS · R01 NS054695 · United States
External Links
PubMed source DOI: 10.1128/JVI.00013-07 PMC Full Text View journal details
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