A novel oncolytic herpes simplex virus armed with the carboxyl-terminus of murine MyD116 has enhanced anti-tumour efficacy against human breast cancer cells

Cheng,Lin; Jiang,Hua; Fan,Jingjing; Wang,Jiani; Hu,Pan; Ruan,Ying; Liu,Renbin

doi:10.3892/ol.2018.8247

A novel oncolytic herpes simplex virus armed with the carboxyl-terminus of murine MyD116 has enhanced anti-tumour efficacy against human breast cancer cells

Authors:
- Lin Cheng
- Hua Jiang
- Jingjing Fan
- Jiani Wang
- Pan Hu
- Ying Ruan
- Renbin Liu
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Affiliations: Breast Cancer Center, Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Breast and Neck Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang 830011, P.R. China
Published online on: March 13, 2018 https://doi.org/10.3892/ol.2018.8247
Pages: 7046-7052
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oncolytic herpes simplex virus-1 (oHSV-1) vectors are promising therapeutic agents for cancer. The deletion of the γ34.5 gene eliminates the neurovirulence but attenuates virus replication at the same time. The carboxyl‑terminus of protein phosphatase 1 regulatory subunit 15A (also known as MyD116/GADD34) is homologous to that of γ34.5; hence, it may substitute for γ34.5 to enhance the replication and cytotoxicity of the virus. To investigate whether the C‑terminus of MyD116 can enhance the anti‑tumour efficacy of G47Δ on human breast cancer cells, a GD116 mutant was constructed by inserting a γ34.5‑MyD116 chimaera into the G47Δ genome using a bacterial artificial chromosome and two recombinase systems (Cre/loxP and FLPE/FRT). A GD‑empty mutant containing only the cytomegalovirus sequence was also created as a control using the same method. Next, the replication and cytotoxicity of these two virus vectors were evaluated in breast cancer cells. Compared with the GD‑empty vector, GD116 possessed an enhanced replication capability and oncolytic activity in MCF‑7 and MDA‑MB‑231 cells. On the fifth day after infection with GD116 at MOIs of 0.01 and 0.1, 49.2 and 82.8% of MCF‑7 cells, respectively, were killed, with 35.0 and 50.2% of MDA‑MB‑231 cells, respectively, killed by GD116 at MOIs of 0.1 and 0.3. Additionally, the insertion of the γ34.5‑MyD116 chimaera promoted virus replication in MDA‑MB‑468 at 48 h after infection, although no increased cytotoxic effect was observed. The findings of the present study indicate that the C terminus of the MyD116 gene can be substituted for the corresponding domain of the γ34.5 gene of oHSV‑1 to promote the replication of the virus in infected cells. Furthermore, the novel virus mutant GD116 armed with a γ34.5‑MyD116 chimaera has enhanced anti‑tumour efficacy against human breast cancer cells in vitro.

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