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Effect of Loss-of-function of the herpes Simplex Virus-1 microRNA h6-5p on Virus Replication

Virologica Sinica 2019年第4期34卷 386-396页

作者： Rongquan huang Xusha Zhou Shuqi Ren Xianjie Liu Zhiyuan han Grace Guoying Zhou School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhou 511436China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

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.

关键词： mir-h6-5p miR-H1-3p Sponge Replication herpes simplex virus-1(hSV-1)

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