Understanding the regulation of translation and replication of Coxsackievirus B3 RNA by host RNA binding proteins

Abstract

Coxsackievirus B3 (CVB3) is an enterovirus, with a positive-sense single-stranded RNA genome. The genome contains a single open reading frame (ORF) flanked by untranslated regions (UTR) at the 5’ and 3’ ends. The viral genomic RNA undergoes translation driven by a type I “Internal Ribosome Entry Site” (IRES) element present in the 5’UTR. The 5’UTR is 741 nucleotides long and encompasses 7 major stem loops (SLs). The SL-I forms a cloverleaf RNA shaped structure, conserved in all enteroviruses, that is primarily required for replication of the virus. SL-II to SL-VI encompasses the IRES element, required for translation of the viral genome. The genome encodes for several viral proteins, including the RNA dependent RNA polymerase 3D, that facilitate viral RNA replication. CVB3 replication is a two-step process. First, the genomic RNA is used as a template to synthesise a negative strand RNA which is then used as a template to synthesize more positive strand RNAs The observations implicate the significance of host RNA binding proteins in influencing CVB3 RNA translation and replication. This study identifies the key players involved in orchestrating the translation and replication of CVB3 RNA and provide mechanistic insights on how they execute their function