Conduits, Doppelgängers, and Chimeras: RNA Structures at the Virus-Host Interface

Viruses and the hosts they parasitize are engaged in a perpetual tug-of-war that is fought at multiple virus-host interfaces from the cell surface to the nucleus. It is increasingly clear that structured RNA elements represent major players and conduits at the forefront of this push and pull. Viral RNA structures hijack or subvert host RNA polymerases; ribosomes; translation-associated enzymes; RNA processing, modification, and transport systems; antiviral immunity proteins; and more. Recent advances in visualizing complex RNA and ribonucleoprotein structures at the virus-host interfaces have provided timely new insights into molecular mechanisms of viral exploitation, host defense, and viral counter-defense. Through the lens of RNA structure and recognition, we compare and analyze a representative set of such interfaces to discern general patterns and recurring strategies. We find that virus-host interfaces frequently have their roots or doppelgängers in the existing cellular interfaces. This suggests widespread viral mimicry of cellular interfaces and interactions. Viral RNAs further borrow and amalgamate distinct features from several host RNAs to form chimeras, which simultaneously target multiple host systems for viral gains.