MicroRNA Antagonism of the Picornaviral Life Cycle: Alternative Mechanisms of Interference

PLoS Pathogens

Bryan R. Cullen¹  Stephen J. Russell²  Elizabeth M. Hadac²  Elizabeth J. Kelly² 

[1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America;Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America

关键词: MicroRNAs;    Viral replication;    Messenger RNA;    Protein translation;    Life cycles;    Cancer treatment;    Viral genomics;    Mouse models;   

DOI  :  10.1371/journal.ppat.1000820

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

In addition to modulating the function and stability of cellular mRNAs, microRNAs can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. To elucidate the mechanisms underlying microRNA-mediated antiviral activity, we modified the 3′ untranslated region (3′UTR) of Coxsackievirus A21 to incorporate targets with varying degrees of homology to endogenous microRNAs. We show that microRNAs can interrupt the picornavirus life-cycle at multiple levels, including catalytic degradation of the viral RNA genome, suppression of cap-independent mRNA translation, and interference with genome encapsidation. In addition, we have examined the extent to which endogenous microRNAs can suppress viral replication in vivo and how viruses can overcome this inhibition by microRNA saturation in mouse cancer models.

【 授权许可】

CC BY