Diverse Strategies Used by Picornaviruses to Escape Host RNA Decay Pathways

Figures

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  Figure 1. Poliovirus interactions with host RNA decay pathways. Picornavirus RNAs are exposed to degradation machinery from multiple RNA decay pathways and processes including 5′→3′ degradation in processing bodies (PBs), 5′→3′ or 3′→5′ degradation by mRNA decay pathways, and endonucleolytic cleavage as a result of activation of the innate immune response or microRNA-mediated decay. Poliovirus RNA serves as a model for the picornavirus genome. Genomic RNA is linked to a small virus-encoded protein, VPg, at the 5′ terminus. The 5′ non-coding region (NCR) contains a cloverleaf structure (CL) and an internal ribosome entry site (IRES). A single open reading frame codes both structural (VP1-4) and non-structural (2A-3D) proteins that are proteolytically processed into precursor and mature viral proteins. The 3′ end of the genome encodes a 3′ NCR and poly(A) tract.

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  Figure 2. Inhibition of ribonuclease L (RNase L) activation by picornavirus proteins. RNase L is an effector molecule of the innate immune response. In its active form, RNase L endonucleolytically cleaves viral RNA (vRNA). Several picornaviruses have been shown to inhibit RNase L directly through binding of a viral inhibitor to RNase L or up-regulation of the cellular RNase L inhibitor, RLI/ABCE. Picornaviruses also indirectly prevent activation of RNase L through extensive disruption of pathways that contribute to the innate immune response. The signaling cascade that is initiated by MDA5 following detection of viral double-stranded RNA is disrupted at multiple steps during infection, which prevents expression of interferon (IFN)-induced genes and activation of RNase L. Additionally, the disassembly of stress granules (SGs) during infection inhibits SG-mediated enhancement of the innate immune response. Simplified pathways are depicted here, highlighting points in the pathway that are inhibited by specific picornaviruses and the viral protein responsible (“?” indicates that the viral protein responsible is unknown). PV, poliovirus; CVA16, coxsackievirus A16; CVB3, coxsackievirus B3; EV71,…

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  Figure 3. Inhibition of PBs and mRNA decay proteins during picornavirus infection. Deadenylation, decapping, and 5′→3′ RNA degradation machinery are targeted during poliovirus (PV) and coxsackievirus B3 (CVB3) infection. The localization of non-translating RNAs and mRNA decay proteins in PBs indicate that these RNA granules may be involved in 5′→3′ mRNA decay. PBs are dispersed during poliovirus and CVB3 infection, thereby disrupting their possible contribution to vRNA degradation. During poliovirus infection, Pan3 and Dcp1a are cleaved by 3C proteinase and Xrn1 is degraded by a proteasome-dependent mechanism.