Infection Dynamics and Genomic Mutations of Hepatitis E Virus in Naturally Infected Pigs on a Farrow-to-Finish Farm in Japan: A Survey from 2012 to 2021

Abstract

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans. Pigs are the primary reservoir for zoonotic HEV genotypes 3 and 4 worldwide. This study investigated the infection dynamics and genomic mutations of HEV in domestic pigs on a farrow-to-finish pig farm in Japan between 2012 and 2021. A high prevalence of anti-HEV IgG antibodies was noted among pigs on this farm in 2012, when the survey started, and persisted for at least nine years. During 2012–2021, HEV RNA was detected in both serum and fecal samples, indicating active viral replication. Environmental samples, including slurry samples in manure pits, feces on the floor, floor and wall swabs in pens, and dust samples, also tested positive for HEV RNA, suggesting potential sources of infection within the farm environment. Indeed, pigs raised in HEV-contaminated houses had a higher rate of HEV infection than those in an HEV-free house. All 104 HEV strains belonged to subgenotype 3b, showing a gradual decrease in nucleotide identities over time. The 2012 (swEJM1201802S) and 2021 (swEJM2100729F) HEV strains shared 97.9% sequence identity over the entire genome. Importantly, the swEJM2100729F strain efficiently propagated in human hepatoma cells, demonstrating its infectivity. These findings contribute to our understanding of the prevalence, transmission dynamics, and genetic characteristics of HEV in domestic pigs, emphasizing the potential risks associated with HEV infections and are crucial for developing effective strategies to mitigate the risk of HEV infection in both animals and humans.

Hepatitis E Virus Infection Caused Elevation of Alanine Aminotransferase Levels in a Patient with Chronic Hepatitis B and Choledocholithiasis

“…HEV genotypes 1 and 2 are clearly responsible for human hepatitis, and they are spread through the fecal-oral route via contaminated water in Asia and Africa and in Africa and Mexico, respectively [7]. The incidence of autochthonous HEV infections (predominantly genotypes 3 and 4) is increasing in industrialized countries such as Japan [25][26][27]. The present case supports the previous reports that HEV genotype 3, as well as other genotypes, can induce acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases [28][29][30].…”

Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection

“…15 HEV infection occurs via intake of grilled or undercooked pork meat and entrails or of game meat contaminated with HEV. 53,54 It has been suggested that transfusion-associated transmission is a potential risk factor for HEV infection. 42 It was reported that a patient was infected with HEV via transfused blood from 23 voluntary do-…”

“…19 Pigs are the primary reservoirs for zoonotic infection of HEV-3 and HEV-4 in Japan. 13,15,20,36,37,40,53,[73][74][75][76][77][78] Wild boars in Japan also serve as reservoirs of HEV-3 and HEV-4. 28,29,79 HEV-3 was found to infect wild sika deer, 26,30,54,80 wild mongooses, 81 rabbits, 82 and monkeys 83 in Japan.…”

Detection and isolation of genotype 3 subtype b hepatitis E viruses from wild boars in Japan

“…1c ). However, BLAST analyses showed that WB0567 shares 91.8% nucleotide sequence identity with the strain JMT-Chiba08L detected in a patient in Chiba Prefecture, 91.0% identity with the strain JHS-Kan06L detected in a patient in Kanagawa Prefecture (LC406572), and 92.1%, 91.3% and 90.6% identity with strains swEJM1201802SC, swEJM2100729FC and swj570 detected in swine in Japan [ 20 ] ( Fig. 1c ).…”