title: A novel fusogenic herpes simplex virus for oncolytic virotherapy of squamous cell carcinoma.
abstract: BACKGROUND
  R849 is a neurovirulent γ₁34.5 gene-deficient form of herpes simplex virus type 1 (HSV-1) and has LacZ genes at the deleted sites of the γ₁34.5 gene. HF is a spontaneously occurring, fusogenic HSV-1 strain. The purpose of this work was to generate a virus that has the syncytial character of HF, while preserving the γ₁34.5 gene inactivation profile of R849 virus.
  
  
  RESULTS
  Vero cells were infected with R849 and HF simultaneously and two viruses, RH1 and RH2, expressing the LacZ gene and inducing extensive cell fusion were selected. A polymerase chain reaction (PCR)-based analysis suggested that one copy of the γ₁34.5 gene is lost in RH1, whereas both copies are lost in RH2, and that the γ₁34.5 gene is replaced by a R849-derived DNA fragment with the LacZ gene. These viruses produced larger plaques and more progeny than the parental viruses. Infection with RH2 decreased the viability of oral squamous cell carcinoma (SCC) cells most strongly. When RH2 was injected into xenografts of oral SCC in nude mice, multinucleated cells were produced and the growth of the tumors was suppressed significantly.
  
  
  CONCLUSIONS
  These results indicate that novel oncolytic HSV-1 vectors can be produced with the genetic background of the oncolytic HSV-1 HF, and that RH2 is deficient in γ₁34.5 genes and shows extensive cytopathic effects in oral SCC cells. RH2 may be useful in oncolytic virotherapy for oral SCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takaoka
authors.forename: Gen
authors.initials: G
authors.lastname: Takahashi
authors.forename: Fumi
authors.initials: F
authors.lastname: Ogawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Imai
authors.forename: Soichi
authors.initials: S
authors.lastname: Iwai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yura
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002522:Chlorocebus aethiops; D005260:Female; D017353:Gene Deletion; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D011995:Recombination, Genetic; D014183:Transplantation, Heterologous / Q000473:pathology; D014709:Vero Cells; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins