Regulation of Ca2+/calmodulin kinase II inhibitor alpha (CaMKIINalpha) in virus-infected mouse brain.

The alpha and beta isoforms of rat Ca(2+)/calmodulin kinase II inhibitor (CaMKIINalpha/beta) expressed in brain or brain and testis, respectively, are potent inhibitors of Ca(2+)/calmodulin kinase II (CaMKII) in vitro. However, the regulation or function of CaMKIINalpha/beta in the central nervous system (CNS) is not known. In this study, we demonstrate that mouse CaMKIINalpha gene encodes a 2.9kb brain-specific transcript whose expression is downregulated in mouse brain during Japanese encephalitis virus (JEV) and rabies virus infection. The downregulation is specific for CaMKIINalpha but not CaMKIINbeta mRNA. In addition to these changes in CaMKIINalpha mRNA, distinct changes are also observed in the phosphorylation as well as subcellular localization of CaMKIIalpha leading to an increase in cytosolic CaMKII activity in JEV-infected mouse brain. The differential regulation of CaMKIIalpha and CaMKIINalpha during JEV infection suggests a possible role for these proteins in viral infection and/or virus-induced neuropathogenesis in the CNS.