PMID- 34424160 OWN - NLM STAT- MEDLINE DCOM- 20210906 LR - 20211006 IS - 1465-2099 (Electronic) IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 102 IP - 8 DP - 2021 Aug TI - A virulent and pathogenic infectious clone of Senecavirus A. LID - 10.1099/jgv.0.001643 [doi] LID - 001643 AB - Senecavirus A (SVA) is a picornavirus that circulates in swine populations worldwide causing vesicular disease (VD) in affected animals. Here we developed a reverse genetics system for SVA based on the well-characterized wild-type SVA strain SD15-26 (wt SVA SD15-26). The full-length cDNA genome of SVA was cloned into a plasmid under a T7 RNA polymerase promoter. Following in vitro transcription, the genomic viral RNA was transfected into BHK-21 cells and rescue of infectious virus (rSVA SD15-26) was shown by inoculation of highly susceptible H1299 cells. In vitro characterization of the rSVA SD15-26 showed similar replication properties and protein expression levels as the wt SVA SD15-26. A pathogenesis study was conducted in 15-week-old finishing pigs to evaluate the pathogenicity and infection dynamics of the rSVA SD15-26 virus in comparison to the wt SVA SD15-26. Animals from both rSVA- and wt SVA SD15-26-inoculated groups presented characteristic SVA clinical signs (lethargy and lameness) followed by the development of vesicular lesions on the snout and/or feet. The clinical outcome of infection, including disease onset, severity and duration was similar in rSVA- and the wt SVA SD15-26-inoculated animals. All animals inoculated with rSVA or with wt SVA SD15-26 presented a short-term viremia, and animals from both groups shed similar amounts of virus in oral and nasal secretion, and faeces. Our data demonstrates that the rSVA SD5-26 clone is fully virulent and pathogenic in pigs, presenting comparable pathogenesis and infection dynamics to the wt SVA SD15-26 strain. The infectious clone generated here is a useful platform to study virulence determinants of SVA, and to dissect other aspects of SVA infection biology, pathogenesis and persistence. FAU - Fernandes, Maureen H V AU - Fernandes MHV AD - Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. AD - Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA. FAU - de Lima, Marcelo AU - de Lima M AD - Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA. AD - Laboratorio de Virologia e Imunologia, Faculdade de Veterinaria, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Joshi, Lok R AU - Joshi LR AD - Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. AD - Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA. FAU - Diel, Diego G AU - Diel DG AD - Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. AD - Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA. LA - eng GR - 2019-67015-29830/National Institute of Food and Agriculture/ PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - Senecavirus A SB - IM MH - Animals MH - Cell Line MH - Cricetinae MH - Humans MH - Picornaviridae/*pathogenicity MH - *Picornaviridae Infections/veterinary/virology MH - Swine MH - Swine Diseases/*virology MH - Viremia/virology MH - Virulence PMC - PMC8489587 OTO - NOTNLM OT - SVA OT - SVV OT - Seneca Valley virus OT - infectious clone OT - recombinant OT - reverse genetics OT - vesicular disease COIS- The authors declare that there are no conflicts of interest. EDAT- 2021/08/24 06:00 MHDA- 2021/09/07 06:00 PMCR- 2021/08/23 CRDT- 2021/08/23 12:19 PHST- 2021/08/23 12:19 [entrez] PHST- 2021/08/24 06:00 [pubmed] PHST- 2021/09/07 06:00 [medline] PHST- 2021/08/23 00:00 [pmc-release] AID - 001643 [pii] AID - 10.1099/jgv.0.001643 [doi] PST - ppublish SO - J Gen Virol. 2021 Aug;102(8):001643. doi: 10.1099/jgv.0.001643.