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

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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.