RNA-Binding Proteins at the Host-Pathogen Interface Targeting Viral Regulatory Elements

Abstract

Viral RNAs contain the information needed to synthesize their own proteins, to replicate, and to spread to susceptible cells. However, due to their reduced coding capacity RNA viruses rely on host cells to complete their multiplication cycle. This is largely achieved by the concerted action of regulatory structural elements on viral RNAs and a subset of host proteins, whose dedicated function across all stages of the infection steps is critical to complete the viral cycle. Importantly, not only the RNA sequence but also the RNA architecture imposed by the presence of specific structural domains mediates the interaction with host RNA-binding proteins (RBPs), ultimately affecting virus multiplication and spreading. In marked difference with other biological systems, the genome of positive strand RNA viruses is also the mRNA. Here we focus on distinct types of positive strand RNA viruses that differ in the regulatory elements used to promote translation of the viral RNA, as well as in the mechanisms used to evade the series of events connected to antiviral response, including translation shutoff induced in infected cells, assembly of stress granules, and trafficking stress.

Arbovirus-vector protein interactomics identifies Loquacious as a co-factor for dengue virus replication in Aedes mosquitoes

“…Viruses recruit host factors for viral replication and several dsRNA binding proteins have been shown to interact with the 3’UTR of flaviviruses [62, 63]. Despite its role as a regulator of RNAi pathways central to antiviral immunity, our work establishes that the RNA binding protein Loqs is hijacked through protein-protein and protein-RNA interactions to promote flavivirus replication in mosquitoes.…”

Picornavirus translation strategies

“…These strategies are in part facilitated by the delocalization of RBPs to the cytoplasm in infected cells, an event that increases the pool of functionally active factors for viral RNA translation. Soon after the discovery of picornavirus IRES elements in 1988 [5,6], it was found that full IRES activity required the action of host factors, as exemplified by the polypyrimidine tract‐binding protein (PTB), poly(rC)‐binding protein 2 (PCBP2), ErbB3‐binding protein 1 (Ebp1, also known as ITAF 45 and PA2G4), or the cold‐shock domain containing E1 (CSDE1, also known as Unr), among others [50–54], reviewed in [38,55].…”

“…There are various examples of RBPs interacting with picornavirus IRES elements, which are proteolyzed during infection, remodeling their activity on translation after cleavage. Among others, known examples include the PTB protein, the far‐upstream element binding protein 2 (FUBP2), FUBP1, the heterogeneous nuclear ribonucleoprotein (hnRNPK), PCBP2, the Ras GTPase SH3 domain binding protein 1 (G3BP1), and Gemin5 (reviewed in [55]). In the case of PTB, the PV 3C protease recognizes the three isoforms of this protein, generating truncated polypeptides that repress PV IRES activity [59].…”

RNA-Binding Proteins as Regulators of Internal Initiation of Viral mRNA Translation

“…Thus, viral IRESs behave as a complex RNA scaffold interacting with specific RBPs, the 40S ribosomal subunit, or with components of the canonical translational apparatus enabling translation initiation [167,168]. For example, the EMCV IRES directly interacts with eIF4G, an interaction enhanced by eIF4A [169,170].…”