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

Abstract

Highlights Proteomic studies have uncovered more than a thousand cellular proteins that are present in the particles of RNA viruses. Strikingly, nearly four hundred of these are RNA-binding proteins (RBPs). Several virion-incorporated RBPs have been shown to regulate viral particle assembly and the initial steps of infection. These host RBPs with regulatory roles in infection represent potential targets for antiviral therapy.

Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection

“…Our studies showed that SINV infection remodels the cellular RBPome and that these changes are critical for viral fitness (Garcia-Moreno et al, 2019). These observations highlight the essential role that RBPs play in regulating the viral life cycle (Dicker et al, 2021;Garcia-Moreno et al, 2018). In the last few years, several approaches have been developed to identify the cellular proteins that interact with viral RNA (Kim et al, 2020a;LaPointe et al, 2018;Ooi et al, 2019;Phillips et al, 2016;Viktorovskaya et al, 2016).…”

“…However, these viral genomes cannot encode all proteins required to accomplish these processes autonomously. To overcome this limitation, viruses hijack cellular RNA-binding proteins (RBPs) (Dicker et al, 2021;Garcia-Moreno et al, 2018). In response, the host cell employs specialized RBPs to detect viral RNAs and intermediates of replication through the recognition of unusual molecular signatures, including tri-phosphate ends, undermethylated cap, and double-stranded RNA (dsRNA) (Habjan and Pichlmair, 2015).…”

Uncovering viral RNA–host cell interactions on a proteome-wide scale

“…It is therefore unsurprising that vRNA hijacks a plethora of cellular RNAbinding proteins (RBPs) to promote viral replication [1]. Cellular RBPs are involved in virtually every step of the viral life cycle, including genome replication, viral protein synthesis, and assembly of virus progeny [2][3][4][5]. Moreover, vRNA is the target of the antiviral innate immune response because it typically contains unusual molecular signatures that can be recognised by specialised RBPs.…”

“…Several canonical RBPs have been mechanistically linked with viral infection [1,5]. However, the recent discovery of hundreds of novel unconventional RBPs suggests that the breadth of interactions that vRNA can establish with the host cell might be broader than previously anticipated [1,5]. As an illustrative example, the E3 ubiquitin ligase TRIM25 participates in the antiviral response mediated by the pattern recognition receptors RIG-I and ZAP [15][16][17], and it was recently identified as an RBP by proteome-wide approaches [9,[18][19][20][21].…”

Alphavirus infection triggers selective cytoplasmic translocation of nuclear RBPs with moonlighting antiviral roles

“…It is thus a hub for crucial host-virus interactions that regulate the viral life cycle (Garcia-Moreno et al, 2018;Iselin et al, 2021). Cellular RNA-binding proteins (RBPs) are indeed involved in virtually every step of alphavirus life cycle, and can play pro-or antiviral roles (Balistreri et al, 2014;Carrasco et al, 2018;Dicker et al, 2020;Garcia-Moreno et al, 2019;Kim et al, 2020). However, the complement of RBPs that engage with viral RNA (vRNA) in infected cells have remained largely unknown.…”