Genomic characterization and recombination analysis of hepatitis E virus in humans and swine across Asia: implications for food safety

Introduction: Hepatitis E virus (HEV) is a globally prevalent zoonotic pathogen posing major public health risks. Swine, a major meat source, carry HEV strains genetically similar to those in humans, highlighting the risk of zoonotic foodborne transmission. This study aimed to investigate the evolutionary history of HEV through phylogenetic and recombination analyses, further provide key reference bases for public health management, improve food safety standards, and offer support for developing effective strategies to prevent foodborne hepatitis E infections. Methods: We analyzed 348 full-length genomes of HEV isolated from humans and pigs in Asia over the past three decades. Phylogenetic analysis was conducted using the neighbor-joining method in MEGA11. Recombination analysis was performed with seven methods in RDP4, and sequence similarity was visualized using Simplot. Results: HEV-4 predominated in Asia, especially China, whereas HEV-3 was regionally endemic. Through genomic analysis, we identified 34 potential natural recombination events, predominantly occurring in the RNA-dependent RNA polymerase (RdRp) region; 14 events occurred between swine and human strains, supporting the hypothesis of cross-species transmission. Moreover, 20 recombination events occurred in China and mainly involved HEV-4 strains, suggesting that HEV has distinct evolutionary dynamics. The detection of five inter-genotypic recombination events may highlight ongoing genetic exchange within HEV populations in Asia, and the biological significance of these events remains to be determined. Discussion: These findings highlight the importance of tracking the evolutionary dynamics of HEV through genomic surveillance, and further underscore the necessity of conducting ongoing HEV surveillance and research to inform prevention strategies.