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

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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

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Y Furukawa1, A Takasu1, Y Yura1

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

Cancer Gene Therapy
|October 7, 2017
PubMed

Insights

Neurovirulence gene-deficient Herpes simplex virus type 1 (HSV-1) strain RH2 effectively triggers programmed cell death in squamous cell carcinoma (SCC) cells. This oncolytic virus induces autophagy, apoptosis, and pyroptosis, offering a potential new avenue for cancer therapy.

Area of Science:

  • Oncolytic virotherapy
  • Cancer biology
  • Molecular virology

Background:

  • Herpes simplex virus type 1 (HSV-1) is extensively researched for oncolytic virotherapy.
  • The precise role of autophagy in programmed cell death induced by neurovirulence gene-deficient HSV-1 in squamous cell carcinoma (SCC) remains unclear.

Purpose of the Study:

  • To investigate the mechanism of cell death induced by the oncolytic HSV-1 strain RH2 in SCC cells.
  • To determine the involvement of autophagy in the oncolytic activity of HSV-1 RH2.

Main Methods:

  • Utilized the γ34.5 gene-deficient HSV-1 strain RH2 for infection of human SCC cells.
  • Monitored viral replication, cell fusion, and cell death markers.
  • Assessed autophagy markers (LC3, Beclin 1) and apoptosis/pyroptosis markers (caspase-3, caspase-1).
  • Employed autophagy inhibitors (3-MA, bafilomycin A1) and caspase inhibitors (z-DEVD-fmk, z-YVAD-fmk) to evaluate their impact on cytotoxicity.

Main Results:

  • HSV-1 RH2 replicated in SCC cells, induced cell fusion, and cell death.
  • Infection led to LC3 aggregation, LC3-I to LC3-II conversion, and double-membrane vacuole formation, indicating autophagy induction.
  • No significant changes in Bcl-2 or Bax expression, but a slight decrease in Beclin 1 was observed.
  • Autophagy and caspase inhibitors significantly reduced RH2-induced cytotoxicity, while not affecting viral replication.

Conclusions:

  • The γ34.5 gene-deficient HSV-1 strain RH2 effectively induces cell death in SCC cells.
  • RH2 triggers a combination of autophagic cell death, apoptosis, and pyroptosis.
  • Autophagy plays a crucial role in the oncolytic efficacy of HSV-1 RH2 against SCC.

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