title: Mouse hepatitis virus infection upregulates genes involved in innate immune responses.
abstract: Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, the time of peak inflammation, reveals robust expression of IFN-γ, IL-12 and mKC. Data suggest that activated microglia and inflammatory mediators contribute to a local CNS microenvironment that regulates viral replication and IFN-γ production during the acute phase of infection, which in turn can cause phagolysosome maturation and phagocytosis of the myelin sheath, leading to demyelination.
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research-Kolkata (IISER-K), Mohanpur, West Bengal, India.
authors.forename: Dhriti
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Kimmel Cancer Centre, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sankar
authors.initials: S
authors.lastname: Addya
authors.affiliation: Scheie Eye Institute and FM Kirby Centre for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Reas S
authors.initials: RS
authors.lastname: Khan
authors.affiliation: Departments of Anatomy, Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Kenyon
authors.affiliation: Departments of Neurology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Choe
authors.affiliation: Departments of Neurology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Cohrs
authors.affiliation: Scheie Eye Institute and FM Kirby Centre for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Shindler
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research-Kolkata (IISER-K), Mohanpur, West Bengal, India.
authors.forename: Jayasri Das
authors.initials: JD
authors.lastname: Sarma
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D006517:Murine hepatitis virus / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D016207:Cytokines