Structures and Functions of Viral 5' Non-Coding Genomic RNA Domain-I in Group-B Enterovirus Infections.

Marie Glenet,Anne-Laure Lebreil,Paul-Antoine Gretteau,Yohan Nguyen,Laurent Andreoletti,Laetitia Heng,Fatma Berri,Domitille Callon

doi:10.3390/v12090919

Marie Glenet, Anne-Laure Lebreil + Show 6 more

Open Access

https://doi.org/10.3390/v12090919

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Abstract

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5′ end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (internal ribosome entry site, IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5′ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I (Retinoic acid inducible gene I) or MDA5 (melanoma differentiation-associated protein 5) receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host–cell interactions driving the development of acute or persistent EV-B infections.

Highlights

Group-B enteroviruses (EV-B) are common human pathogens responsible for a wide range of pathologies such as myocarditis, pancreatitis, hepatitis, or meningitis resulting from acute infections in children and young adults [1,2]
EV-B belong to the Picornaviridae family [8] and the Enterovirus genus is composed of 15 species, classified according to their biological properties and phylogenetic analyses, seven of which are human viruses: EV-A to -D species and three rhinoviruses species (RV-A to -C) (Figure 1) [9,10,11]
The 50 non-coding region (50 NCR) of EV-B is involved in key steps of the viral life cycle

Summary

Introduction

Group-B enteroviruses (EV-B) are common human pathogens responsible for a wide range of pathologies such as myocarditis, pancreatitis, hepatitis, or meningitis resulting from acute infections in children and young adults [1,2]. The 50 NCR is crucial for the initiation of the replication and translation of the viral genome This enteroviral 50 NCR is about 750 nt in length and composed of two secondary structure complexes: the first one is involved in the replication of both viral positive- and negative-strands and is organized in one stem “a” and three stem-loops “b”, “c”, and “d” resulting in a 50 end Cloverleaf-like structure commonly named viral RNA domain-I (Figure 2B). The present review deciphers functional consequences of the natural loss of some viral 50 terminal RNA domain-I secondary structures on the viral RNA replication and on the type I IFN pathway activation in EV-B infected human cells. Natural 50 TD viral genomes resulting in the loss of different structures in the RNA domain-I could be major key players of host–cell interactions driving the development of acute or persistent infections in human target cells

Functional Organization of 50 Terminal EV-B RNA Secondary Structures

Conclusions and Future Directions