Date of Award

1990

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

In vitro primary cultures of glial cells from neonatal rats and mice were established and utilized in an effort to better characterize the virus-cell interactions and host-cell mechanisms controlling coronavirus (CV) infections within the nervous system of rodents.;Primary cerebral explant cultures from mice, containing oligodendrocytes and astrocytes, when infected with CV-JHMV and MHV{dollar}\sb3{dollar} demonstrated no discrimination in cell tropism with both viruses replicating in either cell-type. Induction of oligodendrocyte differentiation with dbcAMP treatment resulted in a profound suppression of CV replication consistent with previous findings on JHMV replication in differentiated rat oligodendrocytes. A possible mechanism for this CV restriction may involve an inhibition of nucleocapsid protein (NC) dephosphorylation occurring within host-cell endosomes during an early stage of virus infection. Preparations of the regulatory subunit of cAMP-dependent protein kinase type 1 (R{dollar}\sb1{dollar}), found in elevated levels in differentiated oligodendrocytes, inhibited an endosomal phosphoprotein phosphatase, which dephosphorylates the NC protein, thereby controlling this enzyme's activity.;Additional studies utilizing primary glial cultures from neonatal SJL mice documented a genetically determined host-cell mechanism controlling CV serotype specific infection. Mixed glial cultures from SJL mice restricted the replication of CV-JHMV and A59 but fully supported the replication of the highly sero-related strain MHV{dollar}\sb3{dollar}. A comparative analysis of the infectious process demonstrated no difference in the early events of virus infection from adsorption to genome transcription but localized the restriction to the intercellular spread or dissemination of the infection from initial foci.

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