Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus

Yoko Ushijima, Chenhong Luo, Fumi Goshima, Yohei Yamauchi, Hiroshi Kimura, Yukihiro Nishiyama

Research output: Contribution to journalArticle (Academic Journal)

41 Citations (Scopus)

Abstract

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. In this study, we 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.

Original languageEnglish
Pages (from-to)142-9
Number of pages8
JournalMicrobes and Infection
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • Amino Acid Substitution
  • Animals
  • Base Sequence
  • Cell Line
  • Cercopithecus aethiops
  • DNA Mutational Analysis
  • DNA, Viral
  • Frameshift Mutation
  • Gene Expression
  • Genome, Viral
  • Herpesvirus 1, Human
  • Molecular Sequence Data
  • Mutation, Missense
  • Recombination, Genetic
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Viral Proteins
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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