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

1. 一种自发发生的单纯疱疹病毒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，但当通过外周感染途径接种小鼠时，在小鼠中高度减弱。近年来的研究表明，HF10是一种很有前景的溶瘤病毒治疗药物。因此，我们对HF10进行了基因组测序，并将其与具有syn+表型的参考菌株HSV-1株17的基因组进行了比较。测序结果覆盖了菌株17所有开放阅读框对应的整个区域，推测菌株17与HF10的氨基酸总体一致性为99.1%，除了3个具有移框突变的基因编码的蛋白。HF10在基因组中存在大量缺失和插入，导致UL43、UL49.5、UL55、UL56和潜伏期相关转录本缺乏功能性表达。此外，HF10中参与合胞体形成调控的基因UL1、UL20、UL22、UL24、UL27和UL53的氨基酸发生了变化。UL1、UL2、UL11、UL44、US1、US7、US8.5、US10和US12编码的蛋白具有较高的差异性。这些数据提供了HF10的遗传背景和对HSV-1复制和致病性的分子机制的深入了解。单纯疱疹病毒（HSV）的UL11和UL51基因编码的膜蛋白被合并到HSV病毒粒子中。UL11被肉豆蔻酸和棕榈酸双酰化，UL51被棕榈酸单酰化。这两种蛋白已被证明参与HSV的包膜和/或出口。在感染和转染的细胞中，野生型UL11蛋白与脂筏相关，而UL51蛋白与脂筏无关。UL11蛋白的双酰化是与筏结合所必需的。它们与脂筏相关的能力可能决定了它们在HSV出口中的作用。

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.