The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity

Abstract

RNA is a central molecule in RNA virus biology due to its dual function as messenger and genome. However, the small number of proteins encoded by viral genomes is insufficient to enable virus infection. Hence, viruses hijack cellular RNA-binding proteins (RBPs) to aid replication and spread. In this review we discuss the 'knowns' and 'unknowns' regarding the contribution of host RBPs to the formation of viral particles and the initial steps of infection in the newly infected cell. Through comparison of the virion proteomes of ten different human RNA viruses, we confirm that a pool of cellular RBPs are typically incorporated into viral particles. We describe here illustrative examples supporting the important functions of these RBPs in viral particle formation and infectivity and we propose that the role of host RBPs in these steps can be broader than previously anticipated. Understanding how cellular RBPs regulate virus infection can lead to the discovery of novel therapeutic targets against viruses.

Keywords: Protein-RNA interaction; RBP; RNA-binding protein; Virus; Virus assembly; Virus infection; Virus replication.

Fig. 1

Infection cycles of positive-sense single-stranded (ss)RNA viruses, negative-sense ssRNA viruses and retroviruses. Each panel shows a highly simplified version since the infection cycles of individual viruses within each group are very diverse. Steps during which cellular RNA-binding proteins could be involved are highlighted in the speech bubbles.

Fig. 2

An overview of virion proteome datasets from human RNA viruses. The inner circle shows the relative number of proteins for retroviruses (Retro), positive-sense ssRNA viruses (+), and negative-sense ssRNA viruses (−). The outer circle shows the relative sizes of individual datasets. A large proportion of the proteins detected in virions have been indicated to be RNA binders (in black) either based on RNA-interactome capture experiments, Gene Ontology terms, or protein domain composition.