Mechanizm of apoptosis and antiapoptosis in herpes simplex virus -infected cells

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The HSV-2 UL14 protein expressing cell line (14/HEp-2) was more resistant to apoptosis induced by osmotic shock and certain drugs than parental cell line. Furthermore, HSV-1 UL14 protein deletion virus (UL14D) showed weaker inhibition of apoptosis compared to the rescued virus UL14R. The protein's anti-apoptotic function may derive from its heat shock protein-like properties.Herpes simplex virus (HSV) is a major neurovirulent pathogen for humans, involved in a broad spectrum of diseases extending from temporal epilepsy to lethal encephalitis. HSV, a large DNA virus, encodes at least 74 different genes. Although about a half of HSV genes are not essential for viral replication in cultured cells, it is speculated that they play significant roles in viral growth, spread, and virulence in vivo. Stereotaxic microinjection of herpes simplex virus (HSV) into the mouse olfactory bulb resulted in infection of neurons of the piriform cortex. Neurons infected with the wildtype HSV showed no evident phosphorylation of c-Jun N-terminal protein kinase (JNK)/c-Jun. In contrast, neurons infected with a US3 gene-disrupted mutant of the L1BR1 virus displayed phosphorylated JNK/c-Jun in a nuclear staining fashion. Induction of neuronal apoptosis by the, wildtype HSV was partially suppressed when compared with that of the L1BR1 virus. A U53-rescued isolate of the L1B(-)11 virus behaved as did the wildtype virus. Collectively, the US3 protein kinase of HSV plays a role in attenuating the virus-induced activation of the JNK signal transduction pathway in the central nervous system and may contribute, at least in part, to controlling neuronal apoptosis.