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

• 来源期刊: 中国病毒学
• 年，卷（期）: 2019,（4）
• 页码范围: 386-396
• 页数: 11页
• 语种: 英文

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.