权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

单纯疱疹病毒感染细胞凋亡及抗凋亡机制

基本信息

批准号：
14370100
负责人：
NISHIYAMA Yukihiro
金额：
$ 8.32万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370100/
关键词：
Apoptosis US3 protein kinase UL14 protein Herpes simplex virus VP16 JNK

项目摘要

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.

表达HSV-2 UL 14蛋白的细胞系（14/HEp-2）对渗透压休克和某些药物诱导的细胞凋亡具有较强的抵抗力。此外，HSV-1 UL 14蛋白缺失病毒（UL 14 D）显示较弱的抑制细胞凋亡相比，拯救病毒UL 14 R。单纯疱疹病毒（Herpessimplexvirus，HSV）是一种重要的神经毒性病原体，可引起从颞叶癫痫到致死性脑炎的多种疾病。HSV是一种大的DNA病毒，编码至少74个不同的基因。尽管约一半的HSV基因对于培养细胞中的病毒复制不是必需的，但推测它们在体内病毒生长、传播和毒力中起重要作用。将单纯疱疹病毒（HSV）立体定向显微注射到小鼠嗅球中，导致梨状皮质神经元感染。野生型HSV感染的神经元没有明显的c-Jun N-末端蛋白激酶（JNK）/c-Jun磷酸化，而L1 BR 1病毒US 3基因破坏的突变体感染的神经元则以核染色的方式显示JNK/c-Jun磷酸化。与L1 BR 1病毒相比，野生型HSV诱导神经细胞凋亡被部分抑制。L1 B（-）11病毒的U 53拯救分离株的行为与野生型病毒相同。总的来说，HSV的US 3蛋白激酶在减弱病毒诱导的中枢神经系统中JNK信号转导途径的活化中起作用，并且可能至少部分地有助于控制神经元凋亡。