The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
文献类型： 外文期刊
作者： Wang, Nana 1 ; Wang, Haiwei 1 ; Shi, Jiabao 1 ; Li, Chen 1 ; Liu, Xinran 2 ; Fan, Junhao 1 ; Sun, Chao 1 ; Cameron, Craig E. 3 ; Qi, Hong 4 ; Yu, Li 1 ;
作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Peoples R China
2.Penn State Univ, Dept Chem, University Pk, PA 16802 USA
3.Univ N Carolina, Dept Microbiol & Immunol, Sch Med, Chapel Hill, NC 27516 USA
4.Harbin Inst Technol, Sch Environm, Key Lab Urban Water Resource & Environm, Harbin 150090, Peoples R China
5.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, Shandong Key Lab Anim Dis Control & Breeding, 202 North Ind Rd, Jinan 250100, Peoples R China
6.Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, New York, NY 10591 USA
关键词： Senecavirus A; IRES; stem-loop I; translation; viral replication; picornavirus
期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）
ISSN：
年卷期： 2021 年 13 卷 11 期
页码：
收录情况： SCI
摘要： 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 0 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.
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