Abstract
Humans are continuously exposed to a wide array of viruses that cause a significant amount of morbidity and mortality worldwide. Over recent years, the evolutionarily conserved host RNA degradation pathway nonsense-mediated decay (NMD) has emerged as a broad antiviral defense mechanism that controls infection of a variety of RNA and DNA viruses. Besides regulating the abundance of host transcripts, NMD directly destabilizes virus genomic RNA, replication intermediates, and viral transcripts to interfere with replication. In turn, viruses have evolved strategies to modulate cellular NMD activity or repurpose NMD factors to facilitate their replication. In this review, we describe our current understanding of the role of NMD in controlling virus infections as well as the strategies employed by viruses to interfere with NMD.