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 <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, the 5′ untranslated region (5’UTR) of SVA contains an internal ribosome entry site (IRES) that initi...
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oai:doaj.org-article:0ad08b4b486b40b9b691671d0815f6d22021-11-25T19:12:55ZThe Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery10.3390/v131121591999-4915https://doaj.org/article/0ad08b4b486b40b9b691671d0815f6d22021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2159https://doaj.org/toc/1999-4915Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, 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.Nana WangHaiwei WangJiabao ShiChen LiXinran LiuJunhao FanChao SunCraig E. CameronHong QiLi YuMDPI AGarticleSenecavirus AIRESstem-loop Itranslationviral replicationpicornavirusMicrobiologyQR1-502ENViruses, Vol 13, Iss 2159, p 2159 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Senecavirus A IRES stem-loop I translation viral replication picornavirus Microbiology QR1-502 |
| spellingShingle |
Senecavirus A IRES stem-loop I translation viral replication picornavirus Microbiology QR1-502 Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| description |
Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, 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 |
article |
| author |
Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu |
| author_facet |
Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu |
| author_sort |
Nana Wang |
| title |
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_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_sort |
stem-loop i of senecavirus a ires is essential for cap-independent translation activity and virus recovery |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/0ad08b4b486b40b9b691671d0815f6d2 |
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