Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses.,Virology Journal

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Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses.
Virology Journal ( IF 4.0 ) Pub Date : 2020-07-10 , DOI: 10.1186/s12985-020-01365-3
Jun-Ting Cheng _{1,

2} , Ying-Ying Wang _{1,

2} , Lin-Zhong Zhu ₃ , Ying Zhang _{1,

2} , Wen-Qi Cai _{1,

2} , Zi-Wen Han _{1,

2} , Yang Zhou _{1,

2} , Xian-Wang Wang _{1,

4} , Xiao-Chun Peng _{1,

5} , Ying Xiang _{1,

2} , Hui-Yu Yang ₆ , Shu-Zhong Cui ₇ , Zhaowu Ma _{1,

2} , Bing-Rong Liu ₆ , Hong-Wu Xin _{1,

2,

8}

Affiliation

Laboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, 434023, Hubei, China.
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, Hubei, China.
Department of Interventional Therapy, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute. 52, Fucheng Road, Haidian District, Beijing, 100142, China.
Department of Laboratory Medicine, School of Basic Medicine, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, 434023, Hubei, China.
Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, Hubei, China.
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
State Key Laboratory of Respiratory Disease, Affiliated Cancer Hospital Institute of Guangzhou Medical University, Guangzhou, 510095, China.
Lianjiang People's Hospital, Guangdong, 524400, China.

Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy. Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection. Our findings have important implication to HSV biology, infection, immunity and oHSVs.

更新日期：2020-07-10

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