MicroRNA screening identifies miR-134 as a regulator of poliovirus and enterovirus 71 infection

MicroRNA 筛选确定 miR-134 是脊髓灰质炎病毒和肠道病毒 71 型感染的调节剂

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作者:Nichole Lynn Orr-Burks, Byoung-Shik Shim, Weilin Wu, Abhijeet A Bakre, Jon Karpilow, Ralph A Tripp

Abstract

MicroRNAs (miRNAs) regulate virus replication through multiple mechanisms. Poliovirus causes a highly debilitating disease and though global efforts to eradicate polio have sharply decreased polio incidence, unfortunately three countries (Afghanistan, Nigeria and Pakistan) remain polio-endemic. We hypothesize that understanding the host factors involved in polio replication will identify novel prophylactic and therapeutic targets against polio and related viruses. In this data set, employing genome wide screens of miRNA mimics and inhibitors, we identified miRNAs which significantly suppressed polio replication. Specifically, miR-134 regulates poliovirus replication via modulation of ras-related nuclear protein (RAN), an important component of the nuclear transport system. MiR-134 also inhibited other Picornaviridae viruses including EV71, a growing concern and a high priority for vaccination in Asian countries like China. These findings demonstrate a novel mechanism for miRNA regulation of poliovirus and other Picornaviridae viruses in host cells, and thereby may provide a novel approach in combating infection and a potential approach for the development of anti-Picornaviridae strategies.

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