Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Construction of an avian hepatitis E virus replicon expressing heterologous genes and evaluation of its potential as an RNA vaccine platform

  • Moon, Hyun-Woo (Department of Veterinary Microbiology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Sung, Haan Woo (Department of Veterinary Microbiology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Park, Jeongho (Department of Veterinary Microbiology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Kwon, Hyuk Moo (Department of Veterinary Microbiology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
  • Received : 2021.02.08
  • Accepted : 2021.03.22
  • Published : 2021.06.30
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Abstract

To evaluate avian hepatitis E virus (aHEV) as an RNA vaccine platform, ORF2 of aHEV was replaced by heterologous genes, such as eGFP and HA-tag, in aHEV infectious cDNA clones. eGFP and HA-tag replicons were expressed in LMH cells. To confirm expression of the heterologous protein, ORF2 was replaced with the antigenic S1 gene of IBV. The IBVS1 replicon was expressed in LMH cells. To our knowledge, this is the first investigation showing the potential as a RNA vaccine platform using an aHEV. In the future, it may be used in the development of RNA vaccines against various pathogens.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2017R1A2B4001847) and 2017 Research Grant from Kangwon National University (No. 520170372).

References

  1. Meng XJ, Shivaprasad HL. Avian Hepatitis E Virus Infections. In: Swayne DE, Boulianne M, Logue CM, McDougald LR, Nair V, Suarez DL, de Wit S, Grimes T, Johnson D, Kromm M, Prajitno TY, Rubinoff I, Zavala G (eds.). Diseases of Poultry. 14th ed. pp. 528-534, John Wiley & Sons, Hoboken (NJ), 2020.
  2. Sun P, Lin S, He S, Zhou EM, Zhao Q. Avian hepatitis E virus: with the trend of genotypes and host expansion. Front Microbiol 2019;10:1696. https://doi.org/10.3389/fmicb.2019.01696
  3. Perri S, Greer CE, Thudium K, Doe B, Legg H, Liu H, Romero RE, Tang Z, Bin Q, Dubensky TW Jr, Vajdy M, Otten GR, Polo JM. An alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol 2003;77:10394-10403. https://doi.org/10.1128/JVI.77.19.10394-10403.2003
  4. Kariko K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 2008;16:1833-1840. https://doi.org/10.1038/mt.2008.200
  5. Kauffman KJ, Webber MJ, Anderson DG. Materials for non-viral intracellular delivery of messenger RNA therapeutics. J Control Release 2016;240:227-234. https://doi.org/10.1016/j.jconrel.2015.12.032
  6. Jackwood MW. Review of infectious bronchitis virus around the world. Avian Dis 2012;56:634-641. https://doi.org/10.1637/10227-043012-Review.1
  7. Park SJ, Lee BW, Moon HW, Sung HW, Yoon BI, Meng XJ, Kwon HM. Construction of an infectious cDNA clone of genotype 1 avian hepatitis E virus: characterization of its pathogenicity in broiler breeders and demonstration of its utility in studying the role of the hypervariable region in virus replication. J Gen Virol 2015;96(Pt 5):1015-1026. https://doi.org/10.1099/vir.0.000045
  8. Moon HW, Sung HW, Kwon HM. Genomic characteristics of natural recombinant infectious bronchitis viruses isolated in Korea. Korean J Vet Res 2019;59:123-132. https://doi.org/10.14405/kjvr.2019.59.3.123
  9. Emerson SU, Nguyen H, Graff J, Stephany DA, Brockington A, Purcell RH. In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein. J Virol 2004;78:4838-4846. https://doi.org/10.1128/JVI.78.9.4838-4846.2004
  10. Schembri L, Dalibart R, Tomasello F, Legembre P, Ichas F, De Giorgi F. The HA tag is cleaved and loses immunoreactivity during apoptosis. Nat Methods 2007;4:107-108. https://doi.org/10.1038/nmeth0207-107
  11. Wang J, Qin Y, Qin H, Liu L, Ding S, Teng Y, Ji J, Qiu L, Jiang P. Simultaneous detection of assembly and disassembly of multivalent HA tag and anti-HA antibody in single in-capillary assay. Electrophoresis 2016;37:2163-2169. https://doi.org/10.1002/elps.201600004
  12. Tyagi S, Korkaya H, Zafrullah M, Jameel S, Lal SK. The phosphorylated form of the ORF3 protein of hepatitis E virus interacts with its non-glycosylated form of the major capsid protein, ORF2. J Biol Chem 2002;277:22759-22767. https://doi.org/10.1074/jbc.M200185200
  13. Korkaya H, Jameel S, Gupta D, Tyagi S, Kumar R, Zafrullah M, Mazumdar M, Lal SK, Xiaofang L, Sehgal D, Das SR, Sahal D. The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK. J Biol Chem 2001;276:42389-42400. https://doi.org/10.1074/jbc.M101546200