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Role of autophagy in oncolytic herpes simplex virus type 1-induced cell death in squamous cell carcinoma cells

Cancer Gene Therapy volume 24, pages 393–400 (2017)Cite this article

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Abstract

Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ34.5 gene and induces the fusion of human SCC cells, was used. RH2 replicated and induced cell death in SCC cells. RH2 infection was accompanied by the aggregation of microtubule-associated protein 1 light chain 3 (LC3) in the cytoplasm, the conversion of LC3-I to LC3-II and the formation of double-membrane vacuoles containing cell contents. No significant changes were observed in the expression of Bcl-2 or Bax, while a slight decrease was observed in that of Beclin 1. The autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin A1, did not affect viral replication, but significantly inhibited the cytotoxicity of RH2. The caspase-3 inhibitor z-DEVD-fmk and caspase-1 inhibitor z-YVAD-fmk also reduced the cytotoxicity of RH2. These results demonstrated that γ34.5 gene-deficient HSV-1 RH2 induced autophagic cell death in SCC cells as well as pyroptosis and apoptosis.

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Acknowledgements

We thank Dr Shintaro Kira for his advice on flow cytometry. This research was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (No. 24390453).

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  1. Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan

    Y Furukawa, A Takasu & Y Yura

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  1. Y Furukawa
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Correspondence to Y Yura.

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Furukawa, Y., Takasu, A. & Yura, Y. Role of autophagy in oncolytic herpes simplex virus type 1-induced cell death in squamous cell carcinoma cells. Cancer Gene Ther 24, 393–400 (2017). https://doi.org/10.1038/cgt.2017.33

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