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Roles of the accessory genes od herpes simplex viruses in their pathogenicity.

单纯疱疹病毒辅助基因在其致病性中的作用。

基本信息

批准号：
16017240
负责人：
NISHIYAMA Yukihiro
金额：
$ 9.22万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017240/
关键词：
herpe simplex virus UL51 UL56 accessory gene UL11 lipid raft 遺伝子機能

项目摘要

1. A spontaneously occurring herpes simplex virus type 1 (HSV-1) mutant, designated HF10, replicates very efficiently and induces extensive cell fusion in most transformed cells as well as Vero cells, but is highly attenuated in mice when inoculated by peripheral routes of infection. Recent studies have shown that HF10 is a promising agent for use in oncolytic virotherapy. We therefore sequenced the genome of HF10 and compared it with that of HSV-1 strain 17, a reference strain with the syn+ phenotype. The sequencing covered whole regions corresponding to all open reading frames of strain 17, and the overall putative amino acid identity between HF10 and strain 17 was 99.1% except for proteins encoded by three genes with frame-shift mutations. HF10 had a number of deletions and insertions in the genome, resulting in the lack of the functional expression of UL43, UL49.5, UL55, UL56 and latency-associated transcripts. Additionally, HF10 had amino acid changes in genes involved in the regulation of syncytium formation, including UL1, UL20, UL22, UL24, UL27 and UL53. The proteins encoded by UL1, UL2, UL11, UL44, US1, US7, US8.5, US10 and US12 exhibited a relatively high divergence. These data provide the genetic background of HF10 and insight into the molecular mechanism of HSV-1 replication and pathogenicity.2. Both UL11 and UL51 genes of herpes simplex virus (HSV) encode membrane proteins which are incorporated into HSV virion. UL11 is dually acylated by myristoic and palmitoic acids and UL51 is monoacylated by palmitoic acid. Both proteins have been shown to be involved in the envelopment and/or egress of HSV. In infected and transfected cells, wild-type UL11 protein was associated with lipid rafts, but UL51 protein was not. The dually acylation of UL11 protein was necessary for the association with rafts. Their abilities to associate with lipid rafts may determine their roles in the egress of HSV.

1.自发性单纯疱疹病毒1型(HSV-1)突变体，命名为HF10，在大多数转化细胞和Vero细胞中非常有效地复制并诱导广泛的细胞融合，但在小鼠中通过外围感染途径接种时高度减弱。最近的研究表明，HF10是一种很有前途的溶瘤病毒治疗药物。因此，我们对HF10的基因组进行了测序，并将其与具有syn+表型的参考毒株HSV-1株17的基因组进行了比较。测序结果覆盖了17号毒株所有开放阅读框对应的完整区域，除3个基因编码的蛋白质发生移码突变外，HF10与17号毒株的氨基酸同源性为99.1%。HF10在基因组中有许多缺失和插入，导致UL43、UL49.5、UL55、UL56和潜伏期相关转录本的功能表达缺失。此外，HF10在参与合胞体形成调控的基因中存在氨基酸变化，包括UL1、UL20、UL22、UL24、UL27和UL53。UL1、UL2、UL11、UL44、US1、US7、US8.5、US10和US12编码的蛋白质具有较高的差异性。这些数据提供了HF10的遗传背景，并深入了解了HSV-1复制和致病的分子机制。单纯疱疹病毒UL11和UL51基因都编码膜蛋白，膜蛋白被整合到HSV病毒粒子中。UL11由肉豆蔻酸和棕榈酸进行双酰化，UL51由棕榈酸进行单酰化。这两种蛋白都被证明参与了单纯疱疹病毒的包膜和/或排泄。在感染和转染组中，野生型UL11蛋白与脂筏相关，而UL51蛋白与脂筏无关。UL11蛋白的双酰化是与RAFT结合所必需的。它们与脂筏结合的能力可能决定了它们在HSV出口中的作用。

项目成果

期刊论文数量（274）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models.

DOI：
发表时间：
2007-06
期刊：
Hepato-gastroenterology
影响因子：
0
作者：
S. Shimoyama;F. Goshima;O. Teshigahara;H. Kasuya;Y. Kodera;A. Nakao;Y. Nishiyama
通讯作者：
S. Shimoyama;F. Goshima;O. Teshigahara;H. Kasuya;Y. Kodera;A. Nakao;Y. Nishiyama

Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates the viral US3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 amd UL31.

单纯疱疹病毒 1 编码的蛋白激酶 UL13 磷酸化病毒 US3 蛋白激酶并调节病毒包膜因子 UL34 和 UL31 的核定位。