A Recombination-resistant Genome for Live Attenuated and Stable PEDV Vaccines by Engineering the Transcriptional Regulatory Sequences

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2023 Nov 16

PMID 37971221

Authors

Xiaoyu Niu

Mingde Liu

Shaomin Yang

Jiayu Xu

Yixuan J Hou

Dongxiao Liu

Qiyi Tang

Hua Zhu

Qiuhong Wang

Affiliations

Soon will be listed here.

Abstract

Coronaviruses are important pathogens of humans and animals, and vaccine developments against them are imperative. Due to the ability to induce broad and prolonged protective immunity and the convenient administration routes, live attenuated vaccines (LAVs) are promising arms for controlling the deadly coronavirus infections. However, potential recombination events between vaccine and field strains raise a safety concern for LAVs. The porcine epidemic diarrhea virus (PEDV) remodeled TRS (RMT) mutant generated in this study replicated efficiently in both cell culture and in pigs and retained protective immunogenicity against PEDV challenge in pigs. Furthermore, the RMT PEDV was resistant to recombination and genetically stable. Therefore, RMT PEDV can be further optimized as a backbone for the development of safe LAVs.

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References

Sawicki S, Sawicki D . Coronaviruses use discontinuous extension for synthesis of subgenome-length negative strands. Adv Exp Med Biol. 1995; 380:499-506. DOI: 10.1007/978-1-4615-1899-0_79. View

Li W, Li H, Liu Y, Pan Y, Deng F, Song Y . New variants of porcine epidemic diarrhea virus, China, 2011. Emerg Infect Dis. 2012; 18(8):1350-3. PMC: 3414035. DOI: 10.3201/eid1808.120002. View

Zuniga S, Sola I, Alonso S, Enjuanes L . Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis. J Virol. 2003; 78(2):980-94. PMC: 368802. DOI: 10.1128/jvi.78.2.980-994.2004. View

Sola I, Moreno J, Zuniga S, Alonso S, Enjuanes L . Role of nucleotides immediately flanking the transcription-regulating sequence core in coronavirus subgenomic mRNA synthesis. J Virol. 2005; 79(4):2506-16. PMC: 546574. DOI: 10.1128/JVI.79.4.2506-2516.2005. View

Niu X, Kong F, Hou Y, Wang Q . Crucial mutation in the exoribonuclease domain of nsp14 of PEDV leads to high genetic instability during viral replication. Cell Biosci. 2021; 11(1):106. PMC: 8182996. DOI: 10.1186/s13578-021-00598-1. View

Wood E . An apparently new syndrome of porcine epidemic diarrhoea. Vet Rec. 1977; 100(12):243-4. DOI: 10.1136/vr.100.12.243. View

Zuker M . Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003; 31(13):3406-15. PMC: 169194. DOI: 10.1093/nar/gkg595. View

Wang D, Fang L, Xiao S . Porcine epidemic diarrhea in China. Virus Res. 2016; 226:7-13. PMC: 7114554. DOI: 10.1016/j.virusres.2016.05.026. View

Pensaert M, de Bouck P . A new coronavirus-like particle associated with diarrhea in swine. Arch Virol. 1978; 58(3):243-7. PMC: 7086830. DOI: 10.1007/BF01317606. View

10.

Oka T, Saif L, Marthaler D, Esseili M, Meulia T, Lin C . Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene. Vet Microbiol. 2014; 173(3-4):258-69. PMC: 7126216. DOI: 10.1016/j.vetmic.2014.08.012. View

11.

Graham R, Becker M, Eckerle L, Bolles M, Denison M, Baric R . A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med. 2012; 18(12):1820-6. PMC: 3518599. DOI: 10.1038/nm.2972. View

12.

Azhar E, El-Kafrawy S, Farraj S, Hassan A, Al-Saeed M, Hashem A . Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014; 370(26):2499-505. DOI: 10.1056/NEJMoa1401505. View

13.

Niu X, Wang Q . Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines. Viruses. 2022; 14(6). PMC: 9227446. DOI: 10.3390/v14061317. View

14.

Hou Y, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon 3rd K . SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2020; 370(6523):1464-1468. PMC: 7775736. DOI: 10.1126/science.abe8499. View

15.

Beall A, Yount B, Lin C, Hou Y, Wang Q, Saif L . Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A. mBio. 2016; 7(1):e01451-15. PMC: 4724997. DOI: 10.1128/mBio.01451-15. View

16.

Hou Y, Wang Q . Emerging Highly Virulent Porcine Epidemic Diarrhea Virus: Molecular Mechanisms of Attenuation and Rational Design of Live Attenuated Vaccines. Int J Mol Sci. 2019; 20(21). PMC: 6862049. DOI: 10.3390/ijms20215478. View

17.

Zhang Q, Shi K, Yoo D . Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1. Virology. 2016; 489:252-68. PMC: 7111358. DOI: 10.1016/j.virol.2015.12.010. View

18.

Jung K, Saif L, Wang Q . Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control. Virus Res. 2020; 286:198045. PMC: 7266596. DOI: 10.1016/j.virusres.2020.198045. View

19.

. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science. 2004; 303(5664):1666-9. DOI: 10.1126/science.1092002. View

20.

Sun R, Cai R, Chen Y, Liang P, Chen D, Song C . Outbreak of porcine epidemic diarrhea in suckling piglets, China. Emerg Infect Dis. 2012; 18(1):161-3. PMC: 3381683. DOI: 10.3201/eid1801.111259. View