Research on molecular mechanisms of induction and suppression of neuronal death by neurovirulent viruses and on virus neuminvasiveness

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1 The association of virus-induced neuronal apoptosis with neuroinvasiveness was investigated in mouse systems.Herpes simplex virus (HSV) attenuates the induction of apoptosis in peripheral nervous systems (olfactory, vomeronasal and trigeminal). But once in the brain the virus induced neuronal apoptosis. Thus, HSV likely suppresses neuronal apoptosis in the periphery to facilitate neuroinvasion into the brain.2 The involvement of MAP kinases in neuronal apoptosis induced by viruses was investigated in mouse systems.Infection of central neurons with neurovirulent influenza A virus (R404BP virus) resulted in phosphorylation of c-Jun N-terminal kinase (JNK) and induced apoptosis. In astrocytes, p38 MAP kinase was phosphorylated, leading to induction of inflammation including TNF production.3 Inhibition of neuronal apoptosis by HSV accessory genes, HS3 and US11, was investigated.Following infection with wildtype HSV, phosphorylation of JNK and resulting apoptosis were attenuated in central neurons. US3-defecient mutant induced neuronal apoptosis, suggesting that US3 protein kinase suppresses JNK activation and induction of apoptosis. US11 did not attenuate induction of apoptosis in our experimental systems. US11 showed intercellular trafficking activity in the mouse brain