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

Abstract Background 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) an...

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Main Authors: Jun-Ting Cheng, Ying-Ying Wang, Lin-Zhong Zhu, Ying Zhang, Wen-Qi Cai, Zi-Wen Han, Yang Zhou, Xian-Wang Wang, Xiao-Chun Peng, Ying Xiang, Hui-Yu Yang, Shu-Zhong Cui, Zhaowu Ma, Bing-Rong Liu, Hong-Wu Xin
Format: Article
Language:English
Published: BMC 2020-07-01
Series:Virology Journal
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12985-020-01365-3
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author Jun-Ting Cheng
Ying-Ying Wang
Lin-Zhong Zhu
Ying Zhang
Wen-Qi Cai
Zi-Wen Han
Yang Zhou
Xian-Wang Wang
Xiao-Chun Peng
Ying Xiang
Hui-Yu Yang
Shu-Zhong Cui
Zhaowu Ma
Bing-Rong Liu
Hong-Wu Xin
author_facet Jun-Ting Cheng
Ying-Ying Wang
Lin-Zhong Zhu
Ying Zhang
Wen-Qi Cai
Zi-Wen Han
Yang Zhou
Xian-Wang Wang
Xiao-Chun Peng
Ying Xiang
Hui-Yu Yang
Shu-Zhong Cui
Zhaowu Ma
Bing-Rong Liu
Hong-Wu Xin
author_sort Jun-Ting Cheng
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions Our findings have important implication to HSV biology, infection, immunity and oHSVs.
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spelling doaj.art-ac1a7ac87c8b4e58b86da9cbbca86d762022-12-21T18:39:11ZengBMCVirology Journal1743-422X2020-07-0117111110.1186/s12985-020-01365-3Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex virusesJun-Ting Cheng0Ying-Ying Wang1Lin-Zhong Zhu2Ying Zhang3Wen-Qi Cai4Zi-Wen Han5Yang Zhou6Xian-Wang Wang7Xiao-Chun Peng8Ying Xiang9Hui-Yu Yang10Shu-Zhong Cui11Zhaowu Ma12Bing-Rong Liu13Hong-Wu Xin14Laboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityDepartment of Interventional Therapy, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute. 52Laboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou UniversityState Key Laboratory of Respiratory Disease, Affiliated Cancer Hospital Institute of Guangzhou Medical UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou UniversityLaboratory of Oncology, School of Basic Medicine, Health Science Center, Yangtze UniversityAbstract Background 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. Methods 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. Results 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. Conclusions Our findings have important implication to HSV biology, infection, immunity and oHSVs.http://link.springer.com/article/10.1186/s12985-020-01365-3HSV-1HSV-2US12ICP47Transcriptional regulation sequence (TRS)Transcriptional regulation factor (TRF)
spellingShingle Jun-Ting Cheng
Ying-Ying Wang
Lin-Zhong Zhu
Ying Zhang
Wen-Qi Cai
Zi-Wen Han
Yang Zhou
Xian-Wang Wang
Xiao-Chun Peng
Ying Xiang
Hui-Yu Yang
Shu-Zhong Cui
Zhaowu Ma
Bing-Rong Liu
Hong-Wu Xin
Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
Virology Journal
HSV-1
HSV-2
US12
ICP47
Transcriptional regulation sequence (TRS)
Transcriptional regulation factor (TRF)
title Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
title_full Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
title_fullStr Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
title_full_unstemmed Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
title_short Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
title_sort novel transcription regulatory sequences and factors of the immune evasion protein icp47 us12 of herpes simplex viruses
topic HSV-1
HSV-2
US12
ICP47
Transcriptional regulation sequence (TRS)
Transcriptional regulation factor (TRF)
url http://link.springer.com/article/10.1186/s12985-020-01365-3
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