Selective Polyprotein Processing Determines Norovirus Sensitivity to Trim7
Meagan E. Sullender, Linley R. Pierce, Mridula Annaswamy Srinivas, Stacey L. Crockett, Bria F. Dunlap, Rachel Rodgers, Lawrence A. Schriefer, Elizabeth A. Kennedy, Brittany Stewart, John G. Doench, Megan T. Baldridge, Robert C. Orchard
Abstract
To maximize a limited genetic capacity, viruses encode polyproteins that can be subsequently separated into individual components by viral proteases. While classically viewed as a means of economy, recent findings have indicated that polyprotein processing can spatially and temporally coordinate the distinct phases of the viral life cycle. Here, we present a function for alternative polyprotein processing centered on immune defense. We discovered that selective polyprotein processing of the murine norovirus polyprotein shields MNV from restriction by the host antiviral protein Trim7. Trim7 can bind the viral protein NS6 but not the viral precursor protein NS6-7. Our findings provide insight into the evolutionary pressures that define patterns of viral polyprotein processing and uncover a trade-off between viral replication and immune evasion.