Key result
Engineering Coxsackievirus A21 with microRNA targets restricted viral replication in cells expressing cognate microRNAs via RNA degradation and translational suppression, though high-level viremia could overcome this restriction in vivo.
Endogenous microRNAs can inhibit picornavirus replication through multiple mechanisms, which can be overcome by microRNA saturation in vivo.
Does not alter current antiviral practice; leaves open microRNA-based strategies for picornaviruses pending clinical validation.
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.
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Kelly et al. (2010) studied Cancer / viral infection. MicroRNA target insertion in Coxsackievirus A21 vs. Wild-type Coxsackievirus A21 or control miRNA was evaluated on Viral replication and cell viability. Engineering Coxsackievirus A21 with microRNA targets restricted viral replication in cells expressing cognate microRNAs via RNA degradation and translational suppression, though high-level viremia could overcome this restriction in vivo.
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