SOCS4 expressed by recombinant HSV protects against cytokine storm in a mouse model

Ren,Shuqi; Chen,Xiaoqing; Huang,Rongquan; Zhou,Grace   Guoying; Yuan,Zhuqing

doi:10.3892/or.2018.6935

SOCS4 expressed by recombinant HSV protects against cytokine storm in a mouse model

Authors:
- Shuqi Ren
- Xiaoqing Chen
- Rongquan Huang
- Grace Guoying Zhou
- Zhuqing Yuan
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Affiliations: Department of Microbiology and Immunology, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China, Immvira Co., Ltd., Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong 518116, P.R. China, Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China
Published online on: December 18, 2018 https://doi.org/10.3892/or.2018.6935
Pages: 1509-1520
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oncolytic viruses are genetically engineered viruses designed for the treatment of solid tumors, and are often coupled with the antitumor immunity of the host. The challenge of using oncolytic herpes simplex virus (oHSV) as an efficacious oncolytic agent is the potential host tissue damage caused by the production of a range of cytokines following intratumoral oHSV injection. An HSV‑suppressor of cytokine signaling 4 (SOCS4) recombinant virus was created to investigate whether it inhibits cytokine storm. Recombinant HSV‑SOCS4 and HSV‑1(F) were used to infect mice, and levels of several representative cytokines, including monocyte chemoattractant protein‑1, interleukin (IL)‑1β, tumor necrosis factor‑α, IL‑6 and interferon γ, in serum and bronchoalveolar lavage fluid (BALF) of infected mice were determined, and immune cells in BALF and spleen were enumerated. Lung damage, virus titers in the lung, body weight and survival rates of infected mice were also determined and compared between the two groups. The cytokine concentration of HSV‑SOCS4‑infected mice was significantly decreased compared with that of HSV‑1(F)‑infected mice in BALF and serum, and a smaller number of cluster of differentiation (CD)11b+ cells of BALF, and CD8+CD62L+ T cells and CD4+CD62L+ T cells of the spleen were also identified in HSV‑SOCS4‑infected mice. HSV‑SOCS4‑infected mice exhibited slight lung damage, a decrease in body weight loss and a 100% survival rate. The results of the present study indicated that SOCS4 protein may be a useful regulator to inhibit cytokine overproduction, and that HSV‑SOCS4 may provide a possible solution to control cytokine storm and its consequences following induction by oncolytic virus treatment.

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