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PMID: 18667505 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brain macrophages/microglia.

Journal of virology ·Vol. 82 ·No. 20 ·2008-10-00 ·Pages 9829-38

Roth-Cross JK, Bender SJ, Weiss SR

Abstract

The coronavirus mouse hepatitis virus (MHV) induces a minimal type I interferon (IFN) response in several cell types in vitro despite the fact that the type I IFN response is important in protecting the mouse from infection in vivo. When infected with MHV, mice deficient in IFN-associated receptor expression (IFNAR(-/-)) became moribund by 48 h postinfection. MHV also replicated to higher titers and exhibited a more broad tissue tropism in these mice, which lack a type I IFN response. Interestingly, MHV induced IFN-beta in the brains and livers, two main targets of MHV replication, of infected wild-type mice. MHV infection of primary cell cultures indicates that hepatocytes are not responsible for the IFN-beta production in the liver during MHV infection. Furthermore, macrophages and microglia, but not neurons or astrocytes, are responsible for IFN-beta production in the brain. To determine the pathway by which MHV is recognized in macrophages, IFN-beta mRNA expression was quantified following MHV infection of a panel of primary bone marrow-derived macrophages generated from mice lacking different pattern recognition receptors (PRRs). Interestingly, MDA5, a PRR thought to recognize primarily picornaviruses, was required for recognition of MHV. Thus, MHV induces type I IFN in macrophages and microglia in the brains of infected animals and is recognized by an MDA5-dependent pathway in macrophages. These findings suggest that secretion of IFN-beta by macrophages and microglia plays a role in protecting the host from MHV infection of the central nervous system.

MeSH Terms
Animals Astrocytes/cytology,metabolism,virology Bone Marrow Cells/cytology,physiology Brain/cytology,physiology,virology Cells, Cultured DEAD-box RNA Helicases/genetics,metabolism Hepatitis, Viral, Animal/immunology Hepatocytes/cytology,metabolism,virology Interferon Type I/immunology Interferon-Induced Helicase, IFIH1 Macrophages/cytology,immunology,virology Mice Mice, Inbred C57BL Mice, Knockout Microglia/cytology,immunology,virology Murine hepatitis virus/genetics,immunology Neurons/cytology,metabolism,virology Receptor, Interferon alpha-beta/genetics,metabolism Receptors, Interleukin-12/genetics,metabolism Virus Replication
Chemicals
Ifnar1 protein, mouse Interferon Type I Receptors, Interleukin-12 Receptor, Interferon alpha-beta Ifih1 protein, mouse DEAD-box RNA Helicases Interferon-Induced Helicase, IFIH1
Authors & Affiliations
3 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.
Bender Susan J
Weiss Susan R
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.01199-08
Published
2008-10-00
Epub
2008-00-30
Pages
9829-38
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2566260
Subset
IM
Grants
NINDS NIH HHS · R01 NS054695 · United States
NINDS NIH HHS · T32 NS007180 · United States
NINDS NIH HHS · NS-07180 · United States
NINDS NIH HHS · NS-54695 · United States
External Links
PubMed source DOI: 10.1128/JVI.01199-08 PMC Full Text View journal details
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