Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
Posted on 2020-07-11 - 16:09
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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Cheng, Jun-Ting; Wang, Ying-Ying; Zhu, Lin-Zhong; Zhang, Ying; Cai, Wen-Qi; Han, Zi-Wen; et al. (2020). Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5056679.v1
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AUTHORS (15)
JC
Jun-Ting Cheng
YW
Ying-Ying Wang
LZ
Lin-Zhong Zhu
YZ
Ying Zhang
WC
Wen-Qi Cai
ZH
Zi-Wen Han
YZ
Yang Zhou
XW
Xian-Wang Wang
XP
Xiao-Chun Peng
YX
Ying Xiang
HY
Hui-Yu Yang
SC
Shu-Zhong Cui
ZM
Zhaowu Ma
BL
Bing-Rong Liu
HX
Hong-Wu Xin