In vivo and in vitro models of demyelinating disease: efficiency of virus spread and formation of infectious centers among glial cells is genetically determined by the murine host.
Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associated with SJL mice was maintained in explanted glial cultures which, by contrast, fully supported a productive infection by the serorelated mouse hepatitis virus type 3. A comparative analysis of the infectious process in glial cell explants from SJL and CD.1 mice helped to define the stage at which restriction is manifested. Cultures of oligodendrocytes and astrocytes from these strains of mice were challenged with JHMV or mouse hepatitis virus type 3, and cell-virus interactions were monitored, including adsorption, uptake of inoculum, transcription, and cell-to-cell dissemination. The sequence of early events from adsorption to genome activation occurred with about equal efficiency with both viruses and genetically different cells, indicating that SJL resistance is not due to any deficiency in specific receptors or penetration of the inoculum or general expression of viral functions. However, intercellular spread of the infection was restricted in SJL glial cells owing to an as yet undefined component. Since cells from (SJL x CD.1)F1 mice were fully susceptible to JHMV, resistance to virus spread must be due to a deficiency in some factor, perhaps a proteolytic activity necessary for dissemination.
Wilson
G A
GA
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Dales
S
S
D000818:Animals; D001253:Astrocytes / Q000382:microbiology; D002460:Cell Line; D003333:Coronaviridae Infections / Q000235:genetics / Q000382:microbiology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000382:microbiology*; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000382:microbiology*; D009836:Oligodendroglia / Q000382:microbiology; D012367:RNA, Viral / Q000096:biosynthesis; D014779:Virus Replication
D012367:RNA, Viral