In Vivo and in Vitro Models of Demyelinating Disease. Possible Relationship between Induction of Regulatory Subunit from cAMP Dependent Protein Kinases and Inhibition of JHMV Replication in Cultured Oligodendrocytes
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Among the parameters controlling Coronavirus (CV) replication within the nervous system of rodents is the state of glial-cell maturation.1,14 Thus differentiation of primary cultures of oligodendrocytes with dibutyryl cAMP (dbcAMP) effectively results in a restriction of CV-JHMV replication. Treatment of cells with dbcAMP, which directly raises the intracellular concentration of cAMP, stimulates the adenylate cyclase system. In primary rat oligodendrocytes stimulation of the adenylate cyclase system results in an induction of the regulatory subunit (R) of cAMP-dependent protein kinase type 1 (PK1).2 It is conceivable that the function of increase in free R1 within host-cells may be related to inhibition of phosphoprotein phosphatases (PPPase), as previously demonstrated in rabbit skeletal muscle with R2 from PK2.6,7. Evidence from our studies indicates that a PPPase may participate in the early stages of CV infection, perhaps during traverse through endosomes of the host.12 The present study was undertaken to ascertain whether the R protein plays any role in restricting JHMV replication in mature glial cells by inhibiting an endosomal PPPase.
KeywordsRegulatory Subunit Demyelinating Disease Rabbit Skeletal Muscle Mouse Hepatitis Virus Dibutyryl cAMP
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