Hepatitis E: A Global Health Concern
Hepatitis E virus (HEV), a small single-stranded RNA virus of the Hepeviridae family, continues to pose a significant public health challenge worldwide. According to recent estimates, HEV causes over 20 million infections annually, resulting in approximately 44,000 deaths. The virus spreads primarily through the fecal-oral route, often via contaminated water.
HEV comprises eight genotypes, of which genotypes one and two are exclusively human-associated. Other genotypes, such as three and four, are zoonotic, frequently transmitted from animals like swine, rabbits, and camelids. In industrialized nations, zoonotic genotypes three and four account for most hepatitis E cases, with rodents occasionally contributing to the spread. The zoonotic potential of rodent-associated HEV has raised concerns about the virus’s ability to cross species barriers and impact human health, prompting deeper scientific investigation.
Breakthrough Study on Rodent-Associated Hepatitis E
A groundbreaking study recently published in Proceedings of the National Academy of Sciences (PNAS) sheds light on the evolutionary drivers of rodent-associated HEV. Researchers analyzed 7.67 million genomic sequences from nonhuman mammals and identified two previously unknown rodent-associated hepeviruses. Additional analysis revealed two genetically related bat-associated hepeviruses.
To further examine the spread of HEV, scientists tested 2,565 liver samples from 108 species of rodents and shrews collected across Africa, Asia, and Latin America between 2011 and 2018. Using reverse transcription-polymerase chain reaction (RT-PCR) assays, they identified 63 positive samples, predominantly from rodents. These samples contained a high viral load, with 24 near-complete hepevirus genomes isolated from rodents, shrews, and bats.
Phylogenetic analyses revealed significant genetic divergence in rodent- and shrew-associated HEV strains compared to human-associated strains. Unlike bats and birds, which hosted limited HEV diversity, rodents emerged as primary sources of viral evolution and cross-species transmission. Notably, genetically divergent hepeviruses were found coexisting in the livers of certain rodents, hinting at the virus’s ability to adapt and recombine within hosts.
Implications and Future Directions
The study underscores rodents’ critical role in the evolutionary history of HEV. Bayesian analyses pinpoint ungulates, such as swine and camelids, as the direct evolutionary origins of human-associated HEV. However, rodents’ long-term association with hepeviruses suggests they facilitated significant cross-order host shifts, making them pivotal in the virus’s adaptation to humans.
Despite its groundbreaking findings, the study faced some limitations, including nonsystematic sampling and RT-PCR-based testing that may have missed highly divergent strains. Nonetheless, the large dataset and robust analyses reinforce its conclusions.
Future research could focus on developing rodent models, such as immunocompetent gerbils, to study HEV transmission and host-pathogen interactions. These models would be instrumental in optimizing prevention and control strategies for HEV, which remains a significant zoonotic threat.
This research not only deepens the understanding of HEV’s origins but also highlights the urgent need for enhanced surveillance of rodent-associated hepeviruses to mitigate their potential public health impact.
