Regulation of Ca²⁺/calmodulin kinase II inhibitor α (CaMKIINα) in virus-infected mouse brain

Abstract

The α and β isoforms of rat Ca²⁺/calmodulin kinase II inhibitor (CaMKIINα/β) expressed in brain or brain and testis, respectively, are potent inhibitors of Ca²⁺/calmodulin kinase II (CaMKII) in vitro. However, the regulation or function of CaMKIINα/β in the central nervous system (CNS) is not known. In this study, we demonstrate that mouse CaMKIINα gene encodes a 2.9 kb brain-specific transcript whose expression is downregulated in mouse brain during Japanese encephalitis virus (JEV) and rabies virus infection. The downregulation is specific for CaMKIINα but not CaMKIINβ mRNA. In addition to these changes in CaMKIINα mRNA, distinct changes are also observed in the phosphorylation as well as subcellular localization of CaMKIIα leading to an increase in cytosolic CaMKII activity in JEV-infected mouse brain. The differential regulation of CaMKIIα and CaMKIINα during JEV infection suggests a possible role for these proteins in viral infection and/or virus-induced neuropathogenesis in the CNS.