The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
Open Access
- 26 October 2021
- Vol. 13 (11), 2159
- https://doi.org/10.3390/v13112159
Abstract
Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the Senecavirus genus. Like in all members of Picornaviridae, the 5′ untranslated region (5’UTR) of SVA contains an internal ribosome entry site (IRES) that initiates cap-independent translation. For example, the replacement of the IRES of foot-and-mouth disease virus (FMDV) with its relative bovine rhinitis B virus (BRBV) affects the viral translation efficiency and virulence. Structurally, the IRES from SVA resembles that of hepatitis C virus (HCV), a flavivirus. Given the roles of the IRES in cap-independent translation for picornaviruses, we sought to functionally characterize the IRES of this genus by studying chimeric viruses generated by exchanging the native SVA IRES with that of HCV either entirely or individual domains. First, the results showed that a chimeric SVA virus harboring the IRES from HCV, H-SVA, is viable and replicated normally in rodent-derived BHK-21 cells but displays replication defects in porcine-derived ST cells. In the generation of chimeric viruses in which domain-specific elements from SVA were replaced with those of HCV, we identified an essential role for the stem-loop I element for IRES activity and recombinant virus recovery. Furthermore, a series of stem-loop I mutants allowed us to functionally characterize discrete IRES regions and correlate impaired IRES activities, using reporter systems with our inability to recover recombinant viruses in two different cell types. Interestingly, mutant viruses harboring partially defective IRES were viable. However, no discernable replication differences were observed, relative to the wild-type virus, suggesting the cooperation of additional factors, such as intermolecular viral RNA interactions, act in concert in regulating IRES-dependent translation during infection. Altogether, we found that the stem-loop I of SVA is an essential element for IRES-dependent translation activity and viral replication.Keywords
Funding Information
- Open Project of State Key Laboratory of Urban Water Resource and Environment from Harbin Institute of Technology (HC202023)
- National Natural Science Foundation of China (32000126)
This publication has 44 references indexed in Scilit:
- Identification of Recombinant Human Rhinovirus A and C in Circulating Strains from Upper and Lower Respiratory InfectionsPLOS ONE, 2013
- Modulation of Translation Initiation Efficiency in Classical Swine Fever VirusJournal of Virology, 2012
- Modification of the Untranslated Regions of Human Enterovirus 71 Impairs Growth in a Cell-Specific MannerJournal of Virology, 2012
- Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: a Picornavirus with a Pestivirus-Like IRESJournal of Virology, 2011
- The HCV IRES pseudoknot positions the initiation codon on the 40S ribosomal subunitRNA, 2010
- Attenuation of Rabies Virus Replication and Virulence by Picornavirus Internal Ribosome Entry Site ElementsJournal of Virology, 2009
- Factor requirements for translation initiation on the Simian picornavirus internal ribosomal entry siteRNA, 2007
- A Distinct Group of Hepacivirus/Pestivirus-Like Internal Ribosomal Entry Sites in Members of DiversePicornavirusGenera: Evidence for Modular Exchange of Functional Noncoding RNA Elements by RecombinationJournal of Virology, 2007
- Hepatitis C virus-related internal ribosome entry sites are found in multiple genera of the family PicornaviridaeJournal of General Virology, 2006
- Pestivirus Internal Ribosome Entry Site (IRES) Structure and Function: Elements in the 5′ Untranslated Region Important for IRES FunctionJournal of Virology, 2002