Abstract
Hepatitis E virus (HEV) can infect humans, pigs, and many other animals, but recombination in HEV has rarely been reported. In the present study, phylogenetic and recombination analysis was performed on 557 complete HEV genome sequences from the GenBank database. A potentially significant quadruple recombination event was identified by recombination detection analysis. The recombinant progeny virus, HEV_32_Manchester_301214, was produced by inter-genotype recombination between the major parent HEPAC-44 and the minor parent HE-JA15-1335. HEV_32_Manchester_301214 and HEPAC-44 belong to genotype 3, while HE-JA15-1335 belongs to genotype 1, and these three strains were all isolated from humans. Three breakpoints of the four recombination events occurred in the ORF2 region, while another occurred in the ORF1 region. This quadruple recombination event was confirmed by phylogenetic analysis. The genotype, host, and recombination regions of the three strains were analyzed, and the analysis results provide valuable information for future research on HEV diversity.
References
Agrawal S, Gupta D, Panda SK (2001) The 3’ end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp). Virology 282:87–101
Ankavay M, Montpellier C, Sayed IM, Saliou JM, Wychowski C, Saas L, Duvet S, Aliouat-Denis CM, Farhat R, de Masson DV, Meuleman P, Dubuisson J, Cocquerel L (2019) New insights into the ORF2 capsid protein, a key player of the hepatitis E virus lifecycle. Sci Rep 9:6243
Cella E, Golkocheva-Markova E, Sagnelli C, Scolamacchia V, Bruni R, Villano U, Ciccaglione AR, Equestre M, Sagnelli E, Angeletti S, Ciccozzi M (2019) Human hepatitis E virus circulation in Bulgaria: deep Bayesian phylogenetic analysis for viral spread control in the country. J Med Virol 91:132–138
Himmelsbach K, Bender D, Hildt E (2018) Life cycle and morphogenesis of the hepatitis E virus. Emerg Microb Infect 7:196
Kanade GD, Pingale KD, Karpe YA (2019) Protein interactions network of hepatitis E virus RNA and polymerase with host proteins. Front Microbiol 10:2501
Kaushik N, Subramani C, Anang S, Muthumohan R, Shalimar NB, Ranjith-Kumar CT, Surjit M (2017) Zinc salts block hepatitis E virus replication by inhibiting the activity of viral RNA-dependent RNA polymerase. J Virol. https://doi.org/10.1128/JVI.00754-17
Luk KC, Coller KE, Dawson GJ, Cloherty GA (2018) Identification of a putative novel genotype 3/rabbit hepatitis E virus (HEV) recombinant. PLoS ONE 13:e0203618
Martin DP, Murrell B, Golden M, Khoosal A, Muhire B (2015) RDP4: detection and analysis of recombination patterns in virus genomes. Virus Evol 1:vev003
Qian Y, Pu X, Yu Y, Yu X, Kong L, Liu L, Wang H, Shen H (2020) Poliovirus serotype 2 and coxsackievirus A promote the natural recombination of poliovirus. J Med Virol 92:263–270
Sridhar S, Lo SK, Xing F, Yang J, Ye H, Chan JF, Teng JL, Huang C, Yip CC, Lau SK, Woo PC (2017) Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection. Emerg Microb Infect 6:e115
van Cuyck H, Fan J, Robertson DL, Roques P (2005) Evidence of recombination between divergent hepatitis E viruses. J Virol 79:9306–9314
van Tong H, Hoan NX, Wang B, Wedemeyer H, Bock CT, Velavan TP (2016) Hepatitis E virus mutations: functional and clinical relevance. EBioMedicine 11:31–42
Wang B, Akanbi OA, Harms D, Adesina O, Osundare FA, Naidoo D, Deveaux I, Ogundiran O, Ugochukwu U, Mba N, Ihekweazu C, Bock CT (2018) A new hepatitis E virus genotype 2 strain identified from an outbreak in Nigeria, 2017. Virol J 15:163
Wang H, Zhang W, Ni B, Shen H, Song Y, Wang X, Shao S, Hua X, Cui L (2010) Recombination analysis reveals a double recombination event in hepatitis E virus. Virol J 7:129
Wang H, Qian Y, Qian C, Dai C, Shen H (2020) Two Natural Recombination gave rise to the Coxsackievirus B3 GV that triggered outbreaks in China in 2006–2012. Medecine et maladies infectieuses 51:81–85
Yu F, Zhu R, Jia L, Song Q, Deng J, Liu L, Zhao L, Qian Y (2020) Sub-genotype change and recombination of coxsackievirus A6s may be the cause of it being the predominant pathogen for HFMD in children in Beijing, as revealed by analysis of complete genome sequences. Int J Infect Dis 99:156–162
Funding
This research was supported by the National Natural Science Foundation of China (Grant no. 81971945), the State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (SKLVEB2019KFKT019), and the Zhenjiang Key Social Development Project (Grant no. SH2018050).
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HS designed this research. SL, HS, MD, HG, and HW performed the data analysis. HS, MC, SL, and XB wrote the manuscript.
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Shen, H., Liu, S., Ding, M. et al. A quadruple recombination event discovered in hepatitis E virus. Arch Virol 166, 3405–3408 (2021). https://doi.org/10.1007/s00705-021-05251-3
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DOI: https://doi.org/10.1007/s00705-021-05251-3