Flu's cues: Exploiting host post-translational modifications to direct the influenza virus replication cycle.

Abstract

Precise coordination of cellular processes requires prompt specification of protein function in response to various stimuli. This specification includes regulating protein abundance, localization, catalysis, and binding. Post-translational modifications (PTMs) provide cells the plasticity for dynamic and reversible control of protein function. Viral infections provide an exciting lens through which to study PTMs, since PTMs contribute to both cellular responses to infection and viral hijacking of the host. PTMs enhance the already multifunctional nature of viral proteins and offer another level of functional diversity within limited genetic space. Influenza virus protein functions are fine-tuned by diverse types of PTMs, including phosphorylation, ubiquitination, SUMOylation, neddylation, ISGylation, glycosylation, ADP-ribosylation, palmitoylation, and acetylation. All of the major viral proteins are subject to at least one type of PTM. Additionally, as influenza viruses encode no known protein-modifying enzymes, all of these PTMs are mediated by host machinery. Here, we use influenza virus and its proteins as exemplars for how PTMs impact virus replication (Fig 1). Open in a separate window Fig 1 Post-translation control of key steps during the influenza virus replication cycle. Simplified diagram of key steps during the influenza virus life cycle highlighting events that are regulated by PTMs to viral or host proteins. The specific modifications, target proteins, and references are listed for each step. Two processes are highlighted in depth; these examples were chosen because the PTMs and causative host enzymes are known and the modifications have discrete effects on replication. In addition, a large number of PTMs have been identified on viral proteins, but no discrete function has yet been assigned [14]. Ac, acetylation; ADPr, ADP-ribosylation; cRNA, plus-sense genomic RNA; dsRNA, double-stranded RNA; Glycos., N-linked glycosylation; ISG15, ISGylation; Nedd8, neddylation; NP, nucleoprotein; NS1, nonstructural protein 1; PO4, phosphorylation; PTM, post-translational modification; RNP, ribonucleoprotein complex; SA, sialic acid; SUMO, SUMOylation; Ub, ubiquitin and ubiquitination; vRNA, minus-sense genomic RNA.