Picornavirus translation strategies

Abstract

The genome of viruses classified as picornaviruses consists of a single monocistronic positive strand RNA. The coding capacity of these RNA viruses is rather limited, and thus, they rely on the cellular machinery for their viral replication cycle. Upon the entry of the virus into susceptible cells, the viral RNA initially competes with cellular mRNAs for access to the protein synthesis machinery. Not surprisingly, picornaviruses have evolved specialized strategies that successfully allow the expression of viral gene products, which we outline in this review. The main feature of all picornavirus genomes is the presence of a heavily structured RNA element on the 5´UTR, referred to as an internal ribosome entry site (IRES) element, which directs viral protein synthesis as well and, consequently, triggers the subsequent steps required for viral replication. Here, we will summarize recent studies showing that picornavirus IRES elements consist of a modular structure, providing sites of interaction for ribosome subunits, eIFs, and a selective group of RNA‐binding proteins.

RNA Structure in the 5′ Untranslated Region of Enterovirus D68 Strains with Differing Neurovirulence Phenotypes

“…Enteroviruses are ubiquitous and prevalent infectious agents with an incredible diversity of viral types, disease manifestations, tissue tropisms and virulence phenotypes [ 35 , 36 , 37 ]. Despite this diversity, all share a genome organization that includes a long and highly structured 5′ UTR that features six RNA domains: an initial domain called the cloverleaf that forms a three-hairpin junction loop (domain I), followed by five domains that form a type 1 IRES (domains II–VI) [ 38 ]. Structural models for this domain organization have been supported by experimental evidence for a few representative enterovirus types, such as poliovirus (PV) [ 39 ], coxsackievirus B3 (CVB3) [ 40 , 41 ] and enterovirus A71 (EV-A71) [ 42 ].…”

Innovation and renovation: FEBS Open Bio in 2023

“…Our second special issue in 2022, published in June, took a broad look at virology under the direction of guest editor Marcelo López‐Lastra. Encarnacion Martinez‐Salas and co‐authors provided an overview of the strategies used by picornaviruses to hijack the cellular machinery to translate viral proteins [ 6 ]. In the second review, Pablo A. González and co‐authors explored the role of HSF1 in viral infections, and whether positive or negative modulation of this protein may have potential for the treatment of viral infections [ 7 ].…”

Host–virus relationships: a sum of many battles

“…The second review from Francisco‐Velilla et al. [7] describes how picornaviruses overcome the asymmetrical competition with cellular mRNA to recruit the host's translational machinery using noncanonical molecular strategies. Picornaviruses have evolved an RNA structure named the internal ribosome entry site to initiate translation independently of factors strictly required by the cellular mRNA, such as the mRNAs 5′cap modification.…”

“…Various strategies used by viruses to usurp the host's translational machinery rely on their ability to modify the cellular environment and repurpose the function of many cellular RNA-binding proteins (RBP) [5,6]. The second review from Francisco-Velilla et al [7] describes how picornaviruses overcome the asymmetrical competition with cellular mRNA to recruit the host's translational machinery using noncanonical molecular strategies. Picornaviruses have evolved an RNA structure named the internal ribosome entry site to initiate translation independently of factors strictly required by the cellular mRNA, such as the mRNAs 5 0 cap modification.…”

“…Picornaviruses have evolved an RNA structure named the internal ribosome entry site to initiate translation independently of factors strictly required by the cellular mRNA, such as the mRNAs 5 0 cap modification. The review also describes how picornaviruses target important initiation factors and subvert and repurpose the use of cellular RBPs, which usually do not function in cellular mRNA translation, to enhance viral protein synthesis [7]. Therefore, during infection, picornaviruses reprogram the host's translational machinery towards the preferential synthesizing viral proteins.…”