Multifunctional Non-Coding RNAs Mediate Latent Infection and Recurrence of Herpes Simplex Viruses

Abstract

Ying Zhang,1– 3,* Li-Si Zeng,4,* Juan Wang,5,* Wen-Qi Cai,2,3 Weiwen Cui,6 Tong-Jun Song,7 Xiao-Chun Peng,2,8 Zhaowu Ma,2,3 Ying Xiang,2,3 Shu-Zhong Cui,4 Hong-Wu Xin2,3 1Department of Gastroenterology, Chun’an County First People’s Hospital (Zhejiang Provincial People’s Hospital Chun’an Branch), Hangzhou, Zhejiang Province, 311700, People’s Republic of China; 2Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei, 434023, People’s Republic of China; 3Department of Molecular Biology and Biochemistry, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei, 434023, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 5Department of Obstetrics and Gynecology, Lianjiang People’s Hospital, Guangdong, 524400, People’s Republic of China; 6Department of Bioengineering, University of California, Berkeley, CA, 94720, USA; 7Department of Neurosurgery, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong Province, 518104, People’s Republic of China; 8Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei, 434023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Wu Xin; Ying XiangLaboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei, 434023, People’s Republic of ChinaTel [phone]; [phone]Fax [phone]Email [email protected]; [email protected]: Herpes simplex viruses (HSVs) often cause latent infection for a lifetime, leading to repeated recurrence. HSVs have been engineered as oncolytic HSVs. The mechanism of the latent infection and recurrence remains largely unknown, which brings great challenges and limitations to eliminate HSVs in clinic and engineer safe oHSVs. Here, we systematically reviewed the latest development of the multi-step complex process of HSV latency and reactivation. Significantly, we first summarized the three HSV latent infection pathways, analyzed the structure and expression of the LAT1 and LAT2 of HSV-1 and HSV-2, proposed the regulation of LAT expression by four pathways, and dissected the function of LAT mediated by five LAT products of miRNAs, sRNAs, lncRNAs, sncRNAs and ORFs. We further analyzed that application of HSV LAT deletion mutants in HSV vaccines and oHSVs. Our review showed that deleting LAT significantly reduced the latency and reactivation of HSV, providing new ideas for the future development of safe and effective HSV therapeutics, vaccines and oHSVs. In addition, we proposed that RNA silencing or RNA interference may play an important role in HSV latency and reactivation, which is worth validating in future.Keywords: non-coding RNA, small RNA, oncolytic virus, herpes simplex virus, HSV, latent infection, latency-associated transcripts, LATs

Keywords

• non-coding rna
• small rna
• oncolytic virus
• herpes simplex virus (hsv)
• latent infection
• latency-associated transcripts (lats).