A novel fusogenic herpes simplex virus for oncolytic virotherapy of squamous cell carcinoma

• Main Authors: Iwai Soichi, Imai Tomoaki, Ogawa Fumi, Takahashi Gen, Takaoka Hiroo, Yura Yoshiaki
• Format: Article
• Language: English
• Published: BMC 2011-06-01
• Series: Virology Journal
• Subjects: herpes simplex virus mutant; oncolytic virotherapy; oral squamous cell carcinoma; cell fusion
• Online Access: http://www.virologyj.com/content/8/1/294

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>