Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication

作     者：Rongquan Huang Xusha Zhou Shuqi Ren Xianjie Liu Zhiyuan Han Grace Guoying Zhou 

作者机构：School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhou 511436China Shenzhen International Institute for Biomedical ResearchShenzhen 518116China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2019年第34卷第4期

页      面：386-396页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 07[理学] 1001[医学-基础医学(可授医学、理学学位)] 

基　　金：supported by grants from Shenzhen Science and Innovation Commission Project Grants JCYJ20170411094933148 Dapeng Research Project Grants KY20160301 to Shenzhen International Institute for Biomedical Research Guangzhou Science and Innovation Commission Project Grants 2016070100039 Guangzhou Education Bureau Project Grants 1201620034 to Guangzhou Medical University 

主　　题：miR-H6-5p miR-H1-3p Sponge Replication Herpes simplex virus-1(HSV-1) 

摘      要：To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27.However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield.Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.