J Cancer 2019; 10(2):430-440. doi:10.7150/jca.29787

Research Paper

Identification of Putative UL54 (ICP27) Transcription Regulatory Sequences Binding to Oct-1, v-Myb, Pax-6 and Hairy in Herpes Simplex Viruses

Ying-Ying Wang1,2,3*, Yan-Ning Lyu4,*, Hong-Yi Xin5,*, Jun-Ting Cheng1,2,3, Xiao-Qin Liu1,2,6, Xian-Wang Wang1,2,7, Xiao-Chun Peng1,2,8, Ying Xiang1,2,3, Victoria W. Xin9, Cheng-Biao Lu10, Bo-Xu Ren1,8, Yan-Fang Liang11, Jia-Fu Ji12, Zhaowu Ma1,2,3✉, Shu-Zhong Cui13✉, Hong-Wu Xin1,2,3✉

1. The First School of Clinical Medicine, Department of Medicine, Yangtze University, Jingzhou, Hubei 434023, China
2. Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China
3. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China
4. Institute for Infectious Diseases and Endemic Diseases Prevention and Control, Beijing Center for Diseases Prevention and Control, Beijing, 100013, China
5. Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604
6. Department of Medical Imaging, School of Basic Medicine, Yangtze University, Jingzhou, Hubei 434023, China
7. Department of Laboratory Medicine, School of Basic Medicine, Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China
8. Department of Pathophysiology, School of Basic Medicine, Yangtze University, Jingzhou, Hubei 434023, China
9. Montgomery Blair High School Magnet Program Class of 2020, Silver Spring, MD 20901-2451, USA
10. Laboratory of Neuronal Network and Brain Diseases Modulation, School of Medicine, Yangtze University, Jingzhou, Hubei Province, China
11. Department of Radiology, Guangzhou Medical University Cancer Hospital, Guangzhou, China
12. Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
13. Department of Theromotherapy, Guangzhou Medical University Cancer Hospital, Guangzhou, China
*These authors contributed equally to this work.

Abstract

An oncolytic herpes simplex virus (oHSV) has proven amenable in oncolytic virotherapy and was approved to treat melanoma. The immediate-early (IE) protein ICP27 encoded by gene UL54 is essential for HSV infection. Post-transcriptional modification of UL54 would increase tumor targeting of oHSVs. However, UL54 gene transcription regulatory sequences and factors were not reported yet. Here we isolated a new strain LXMW of type 1 HSV (HSV-1-LXMW) in China and found it's closely related to HSV-1 strains Patton and H129 in the US by the first and next generation DNA sequencing viral DNA phylogenetic analysis. Using a weight matrix-based program Match, we found the UL54 transcription regulatory sequences binding to the transcription factors Oct-1, v-Myb and Pax-6 in HSV-1-LXMW, while the sequences binding to Oct-1 and Hairy in a HSV-2 strain. Further validation showed that HSV-1 and HSV-2 shared the common sequence binding to Oct-1, but had unique sequences to bind v-Myb and Pax-6, or Hairy, respectively, by DNA sequence alignment of total 11 HSV strains. The published results howed that the expression of transcription factors is consistent with the tissue tropism of HSV-1 and HSV-2. In the current article a new HSV-1 strain LXMW was isolated and its putative HSV UL54 transcription regulatory sequences and factors were identified for the first time. Our findings highlight the new understanding of the principles of transcriptional regulation in HSV biology and oncolytic virotherapy.

Keywords: Oncolytic Herpes Simplex Virus (oHSV), Long Unique Region 54 (UL54), Infected Cell Polypeptide 27 (ICP27), Transcription Regulatory Sequence, Transcription Factor (TF), RNA polymerase II (RNAP II)

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How to cite this article:
Wang YY, Lyu YN, Xin HY, Cheng JT, Liu XQ, Wang XW, Peng XC, Xiang Y, Xin VW, Lu CB, Ren BX, Liang YF, Ji JF, Ma Z, Cui SZ, Xin HW. Identification of Putative UL54 (ICP27) Transcription Regulatory Sequences Binding to Oct-1, v-Myb, Pax-6 and Hairy in Herpes Simplex Viruses. J Cancer 2019; 10(2):430-440. doi:10.7150/jca.29787. Available from http://www.jcancer.org/v10p0430.htm