Functional and Mechanistic Interplay of Host and Viral Alternative Splicing Regulation during Influenza Infection.

Alternative splicing is a pervasive gene regulatory mechanism utilized by both mammalian cells and viruses to expand their genomic coding capacity. The process of splicing and the RNA sequences that guide this process are the same in mammalian and viral transcripts; however, viruses lack the splicing machinery and therefore must usurp both the host spliceosome and many of the associated regulatory proteins in order to correctly process their genes. Here, we use the example of the influenza A virus to both describe how viruses utilize host splicing factors to regulate their own splicing and provide examples of how viral infection can, in turn, alter host splicing. Importantly, we show that at least some of the viral-induced changes in host splicing occur in genes that alter the efficiency of influenza replication. We emphasize the importance of increased understanding of the mechanistic interplay between host and viral splicing, and its functional consequences, in uncovering potential antiviral vulnerabilities.