Pathogenesis of murine coronavirus in the central nervous system.
Murine coronavirus (mouse hepatitis virus, MHV) is a collection of strains that induce disease in several organ systems of mice. Infection with neurotropic strains JHM and A59 causes acute encephalitis, and in survivors, chronic demyelination, the latter of which serves as an animal model for multiple sclerosis. The MHV receptor is a carcinoembryonic antigen-related cell adhesion molecule, CEACAM1a; paradoxically, CEACAM1a is poorly expressed in the central nervous system (CNS), leading to speculation of an additional receptor. Comparison of highly neurovirulent JHM isolates with less virulent variants and the weakly neurovirulent A59 strain, combined with the use of reverse genetics, has allowed mapping of pathogenic properties to individual viral genes. The spike protein, responsible for viral entry, is a major determinant of tropism and virulence. Other viral proteins, both structural and nonstructural, also contribute to pathogenesis in the CNS. Studies of host responses to MHV indicate that both innate and adaptive responses are crucial to antiviral defense. Type I interferon is essential to prevent very early mortality after infection. CD8 T cells, with the help of CD4 T cells, are crucial for viral clearance during acute disease and persist in the CNS during chronic disease. B cells are necessary to prevent reactivation of virus in the CNS following clearance of acute infection. Despite advances in understanding of coronavirus pathogenesis, questions remain regarding the mechanisms of viral entry and spread in cell types expressing low levels of receptor, as well as the unique interplay between virus and the host immune system during acute and chronic disease.
Bender
Susan J
SJ
Department of Microbiology, University of Pennsylvania School of Medicine, 36th Street and Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Weiss
Susan R
SR
D000818:Animals; D001921:Brain / Q000821:virology; D002272:Carcinoembryonic Antigen / Q000502:physiology; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000821:virology*; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology*; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D015213:Neuroimmunomodulation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D056189:Viral Tropism / Q000502:physiology
D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D014764:Viral Proteins