Cargando…

The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Nana, Wang, Haiwei, Shi, Jiabao, Li, Chen, Liu, Xinran, Fan, Junhao, Sun, Chao, Cameron, Craig E., Qi, Hong, Yu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619302/
https://www.ncbi.nlm.nih.gov/pubmed/34834966
http://dx.doi.org/10.3390/v13112159
_version_ 1784604958117593088
author Wang, Nana
Wang, Haiwei
Shi, Jiabao
Li, Chen
Liu, Xinran
Fan, Junhao
Sun, Chao
Cameron, Craig E.
Qi, Hong
Yu, Li
author_facet Wang, Nana
Wang, Haiwei
Shi, Jiabao
Li, Chen
Liu, Xinran
Fan, Junhao
Sun, Chao
Cameron, Craig E.
Qi, Hong
Yu, Li
author_sort Wang, Nana
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8619302
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86193022021-11-27 The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery Wang, Nana Wang, Haiwei Shi, Jiabao Li, Chen Liu, Xinran Fan, Junhao Sun, Chao Cameron, Craig E. Qi, Hong Yu, Li Viruses Article 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. MDPI 2021-10-26 /pmc/articles/PMC8619302/ /pubmed/34834966 http://dx.doi.org/10.3390/v13112159 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Nana
Wang, Haiwei
Shi, Jiabao
Li, Chen
Liu, Xinran
Fan, Junhao
Sun, Chao
Cameron, Craig E.
Qi, Hong
Yu, Li
The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title_full The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title_fullStr The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title_full_unstemmed The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title_short The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
title_sort stem-loop i of senecavirus a ires is essential for cap-independent translation activity and virus recovery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619302/
https://www.ncbi.nlm.nih.gov/pubmed/34834966
http://dx.doi.org/10.3390/v13112159
work_keys_str_mv AT wangnana thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT wanghaiwei thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT shijiabao thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT lichen thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT liuxinran thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT fanjunhao thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT sunchao thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT cameroncraige thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT qihong thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT yuli thestemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT wangnana stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT wanghaiwei stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT shijiabao stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT lichen stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT liuxinran stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT fanjunhao stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT sunchao stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT cameroncraige stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT qihong stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery
AT yuli stemloopiofsenecavirusairesisessentialforcapindependenttranslationactivityandvirusrecovery