Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brain macrophages/microglia.
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.
Roth-Cross
Jessica K
JK
Department of Microbiology, University of Pennsylvania, School of Medicine, 36th Street and Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Bender
Susan J
SJ
Weiss
Susan R
SR
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology / Q000821:virology; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D006524:Hepatitis, Viral, Animal / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D007370:Interferon Type I / Q000276:immunology*; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D053707:Receptors, Interleukin-12; D053633:Receptor, Interferon alpha-beta; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1