Use of immuno-dominant epitope derived from genotype 4 as a diagnostic reagent for detecting the antibodies against Hepatitis E Virus

The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0·8×10−3 nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork.

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Synthetic Peptides Containing Three Neutralizing Epitopes of Genotype 4 Swine Hepatitis E Virus ORF2 induced Protection against Swine HEV Infection in Rabbit

Vaccines ◽

10.3390/vaccines8020178 ◽

2020 ◽

Vol 8 (2) ◽

pp. 178

Author(s):

Yiyang Chen ◽

Tianxiang Chen ◽

Yuhang Luo ◽

Jie Fan ◽

Meimei Zhang ◽

...

Keyword(s):

Hepatitis E Virus ◽

Keyhole Limpet Hemocyanin ◽

Hepatitis E ◽

Genotype 4 ◽

Virus Shedding ◽

Fecal Shedding ◽

Orf2 Protein ◽

Swine Hepatitis ◽

Phosphate Buffered Saline ◽

Neutralizing Epitopes

Genotype 4 hepatitis E virus (HEV) is a zoonotic pathogen transmitted to humans through food and water. Previously, three genotype 4 swine HEV ORF2 peptides (407EPTV410, 410VKLYTS415, and 458PSRPF462) were identified as epitopes of virus-neutralizing monoclonal antibodies that partially blocked rabbit infection with swine HEV. Here, individual and tandem fused peptides were synthesized, conjugated to keyhole limpet hemocyanin (KLH), then evaluated for immunoprotection of rabbits against swine HEV infection. Forty New Zealand White rabbits were randomly assigned to eight groups; groups 1 thru 5 received three immunizations with EPTV-KLH, VKLYTS-KLH, PSRPF-KLH, EPTVKLYTS-KLH, or EPTVKLYTSPSRPF-KLH, respectively; group 6 received truncated swine HEV ORF2 protein (sp239), and group 7 received phosphate-buffered saline. After an intravenous swine HEV challenge, all group 7 rabbits exhibited viremia and fecal virus shedding by 2–4 weeks post challenge (wpc), seroconversion by 4–9 wpc, elevated alanine aminotransferase (ALT) at 2 wpc, and severe liver lymphocytic venous periphlebitis. Only 1–2 rabbits/group in groups 1–4 exhibited delayed viremia, fecal shedding, seroconversion, increased ALT levels, and slight liver lymphocytic venous periphlebitis; groups 5–6 showed no pathogenic effects. Collectively, these results demonstrate that immunization with a polypeptide containing three genotype 4 HEV ORF2 neutralizing epitopes completely protected rabbits against swine HEV infection.

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