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

The alpha and beta isoforms of rat Ca2+/calmodulin kinase II inhibitor (CaMKIIN alpha/beta) 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 CaMKIIN alpha/beta in the central nervous system (CNS) is not known. In this study, we demonstrate that mouse CaMKIIN alpha 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 CaMKIIN alpha but not CaMKIIN beta mRNA. In addition to these changes in CaMKIIN alpha mRNA, distinct changes are also observed in the phosphorylation as well as subcellular localization of CaMKII alpha leading to an increase in cytosolic CaMKII activity in JEV-infected mouse brain. The differential regulation of CaMKII alpha and CaMKIIN alpha during JEV infection suggests a possible role for these proteins in viral infection and/or virus-induced neuropathogenesis in the CNS. (c) 2006 Elsevier Inc. All rights reserved.