https://scholars.lib.ntu.edu.tw/handle/123456789/550775
標題: | Investigation of the role of the spike protein in reversing the virulence of the highly virulent Taiwan porcine epidemic diarrhea virus Pintung 52 strains and its attenuated counterpart | 作者: | Kao, C.-F. HUI-WEN CHANG |
關鍵字: | Attenuation; PEDV; Reverse genetics; Spike protein; Virulent determinant | 公開日期: | 2019 | 卷: | 12 | 期: | 1 | 來源出版物: | Viruses | 摘要: | Porcine epidemic diarrhea virus (PEDV) has continuously caused severe economic losses to the global swine industries; however, no successful vaccine against PEDV has been developed. In this study, we generated four autologous recombinant viruses, including the highly virulent iPEDVPT-P5, attenuated iPEDVPT-P96, and two chimeric viruses (iPEDVPT-P5-96S and iPEDVPT-P96-5S) with the reciprocally exchanged spike (S) gene, to study the role of the S gene in PEDV pathogenesis. A deeper understanding of PEDV attenuation will aid in the rational design of a live attenuated vaccine (LAV) using reverse genetics system. Our results showed that replacing the S gene from the highly virulent iPEDVPT-P5 led to complete restoration of virulence of the attenuated iPEDVPT-P96, with nearly identical viral shedding, diarrhea pattern, and mortality rate as the parental iPEDVPT-P5. In contrast, substitution of the S gene with that from the attenuated iPEDVPT-P96 resulted in partial attenuation of iPEDVPT-P5, exhibiting similar viral shedding and diarrhea patterns as the parental iPEDVPT-P96 with slightly severe histological lesions and higher mortality rate. Collectively, our data confirmed that the attenuation of the PEDVPT-P96 virus is primarily attributed to mutations in the S gene. However, mutation in S gene alone could not fully attenuate the virulence of iPEDVPT-P5. Gene (s) other than S gene might also play a role in determining virulence. ? 2019 by the authors |
URI: | https://www.scopus.com/inward/record.url?eid=2-s2.0-85077542676&partnerID=40&md5=ddb87982681174406a3b2edd7ede814a https://scholars.lib.ntu.edu.tw/handle/123456789/550775 |
DOI: | 10.3390/v12010041 | SDG/關鍵字: | virus spike protein; coronavirus spike glycoprotein; live vaccine; virus vaccine; amino acid sequence; amino acid substitution; animal cell; animal experiment; animal model; animal tissue; Article; controlled study; diarrhea; gene mutation; gene sequence; histopathology; immunofluorescence; immunohistochemistry; mortality rate; nonhuman; nucleotide sequence; piglet; Porcine epidemic diarrhea virus; Porcine epidemic diarrhea virus pintung 5; Porcine epidemic diarrhea virus pintung 52; Porcine epidemic diarrhea virus pintung 96; real time polymerase chain reaction; S gene; sequence analysis; syncytium; viral plaque assay; virus gene; virus morphology; virus shedding; virus titration; virus virulence; animal; Chlorocebus aethiops; Coronavirus infection; feces; genetics; mutation; pathogenicity; pig; Porcine epidemic diarrhea virus; reverse genetics; swine disease; Taiwan; Vero cell line; virology; virulence; Animals; Chlorocebus aethiops; Coronavirus Infections; Diarrhea; Feces; Mutation; Porcine epidemic diarrhea virus; Reverse Genetics; Spike Glycoprotein, Coronavirus; Swine; Swine Diseases; Taiwan; Vaccines, Attenuated; Vero Cells; Viral Vaccines; Virulence; Virus Shedding |
顯示於: | 分子暨比較病理生物學研究所 |
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