Abstract
Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS.
Highlights
Coronaviruses are a family of large positive-sense RNA viruses that cause a wide range of veterinary and human diseases
The use of reverse genetics to construct recombinant viruses has enabled our lab and others to investigate the interactions between virus and host and identify important virulence factors leading to central nervous system (CNS) and liver disease [1]
The type I interferon response is clearly crucial for defense against mouse hepatitis virus (MHV) infection of the two major target organs, the central nervous system and the liver, as evidenced by uncontrolled replication and accelerated mortality in MHV infected mice lacking the IFNAR
Summary
Coronaviruses are a family of large positive-sense RNA viruses that cause a wide range of veterinary and human diseases. As suggested by Zurney et al [56], cell-type differences in initial responses to virus infection may depend to some degree on basal expression levels of IFN signaling molecules and transcriptions factors involved in the IFN response.
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