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

表达HSV-2UL14蛋白的细胞株(14/Hep-2)对渗透压休克和某些药物诱导的细胞凋亡的抵抗力高于亲本细胞系。此外，HSV-1 UL14蛋白缺失病毒(UL14D)对细胞凋亡的抑制作用弱于被拯救的UL14R病毒。单纯疱疹病毒(HSV)是一种主要的神经毒性病原体，涉及从颞叶癫痫到致死性脑炎的广泛疾病。HSV是一种大型DNA病毒，编码至少74种不同的基因。尽管大约一半的HSV基因对病毒在培养细胞中的复制不是必需的，但人们推测它们在体内对病毒的生长、传播和毒力起着重要作用。单纯疱疹病毒(HSV)立体定向注射到小鼠嗅球，可导致梨状皮质神经元感染。野生型HSV感染的神经元未见明显的c-jun氨基末端蛋白激酶(JNK)/c-jun的磷酸化。相反，被US3基因破坏的L1BR1病毒突变体感染的神经元以核染色的方式显示出磷酸化的JNK/c-Jun。与L1BR1病毒相比，野生型HSV对神经细胞凋亡的诱导作用受到部分抑制。一个U53拯救的L1B(-)11病毒分离株的表现与野生型病毒一样。总之，HSV的US3蛋白激酶在减弱病毒诱导的中枢神经系统JNK信号转导通路的激活中发挥作用，并可能至少部分地有助于控制神经元的凋亡。

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.