Rat hepatitis E virus is circulating widely in French city rats

Rat hepatitis E virus is not confined to isolated pockets of infection. In brown rats sampled across eight French cities between 2021 and 2023, viral RNA turned up in 209 of 686 livers, a 30.5% positivity rate with a 95% confidence interval of 27.1% to 34.0%. Positive animals were found in every city and in every habitat type sampled, from urban parks to sewers and social housing areas. The pattern fits an enzootic virus maintaining itself quietly in dense urban rat populations rather than appearing as a sporadic spillover event.

The finding has direct zoonotic relevance because rat hepatitis E virus, or rHEV, is already linked to human disease. Hepatitis E usually presents as an acute, self-limited infection, yet it can progress to fulminant hepatitis and can become chronic in immunocompromised patients. In that setting, an urban reservoir with a substantial infection burden matters clinically, especially when human exposure may be indirect and unrecognized.

One sentence captures the signal plainly: the virus is established in city rats.

Infection burden rose sharply with body weight

The clearest biological gradient in the dataset came from body weight, used as a proxy for age progression. Rats weighing less than 100 g had a positivity rate of 9.0% (95% CI 5.8%–13.8%), while rats at 100 g had a positivity rate of 40.7% (95% CI 36.3%–45.2%). That difference suggests accumulating exposure over time, with older or larger rats more likely to have acquired infection and carried viral RNA in the liver. Sex did not significantly change positivity.

This age-linked pattern is exactly what an enzootic rodent virus should look like. As rats move through shared burrows, drainage systems, refuse sites, and urban green spaces, repeated contact with contaminated material becomes more likely. A liver-positive rate that rises with body weight is consistent with sustained circulation within colonies rather than a brief epizootic wave.

Habitat also shaped the numbers. Positivity was around 9.7% in urban parks, compared with roughly 44% in sewers and social housing areas. Sewer networks and built residential environments create the kind of sheltered, high-contact ecology that allows a fecal-oral virus or a virus spread through close rodent interactions to persist. Urban parks still harbored infection, but at a far lower rate, suggesting that the structure of the rat population and its access to food, water, and shelter likely influences transmission intensity.

Liver RNA and antibodies tell different parts of the same story

The molecular and serologic results pointed in the same direction. Investigators detected rHEV RNA in liver samples from 209 animals and HEV antibodies in 144 of 317 serum specimens, a seropositivity rate of 45.0% (95% CI 40.0%–51.0%). RNA in tissue indicates current or recent infection, while antibodies reflect prior exposure and immune response. Seen together, those two readouts suggest that a large share of the rat population has encountered the virus at some point, and a substantial fraction is actively infected when sampled.

The serology assay was adapted from a human HEV test and used pE2 as a capture antigen, which allows detection of cross-reactive antibody responses. In practice, that broadens the net for exposure history, though it also means interpretation should stay anchored to the study design and assay characteristics. Even with that caution, the combination of RNA and antibody evidence strengthens the case for long-term circulation in these urban rat communities.

Genome sequencing showed diverse strains and close human-rat similarity

Whole-genome sequencing was performed on 22 rHEV-positive liver samples, yielding 20 full genome sequences with distinct strains. Phylogenetic analysis placed the French sequences within the wider diversity of Rocahepevirus and showed high genetic identity between rat and human sequences in France and elsewhere in Europe. The genomic signal matters because it narrows the evolutionary gap between reservoir and patient isolates. When rat and human sequences align closely, the molecular distance needed to support zoonotic transmission becomes much smaller.

The virus itself belongs to the genus Rocahepevirus, specifically Rocahepevirus ratti, and is phylogenetically distinct from the better-known human HEV species in Paslahepevirus. Even so, human cases have already been documented in multiple regions, including France, Hong Kong, Asia, North America after infection in Central Africa, and Europe. The French rat data do not prove transmission, but they do show that the reservoir is widespread and genetically connected to strains recovered from people.

What the French surveillance adds to zoonotic risk assessment

The study provides baseline data from eight large cities—Paris, Nantes, Lyon, Strasbourg, Bordeaux, Besançon, Nancy, and Marseille—sampled across April 2021 through July 2023. That geographic spread matters because it shows the signal is not limited to a single municipal rodent population. Brown rats were positive in all cities sampled, and the infection burden was high enough to suggest stable maintenance across urban settings.

From a public health perspective, the findings sharpen several practical concerns. First, rats are not a peripheral host; they appear to be a durable reservoir. Second, people living or working in sewer systems, dense housing areas, or environments with heavy rat activity may face repeated exposure even without direct animal contact. Third, because human rHEV infection can present as persistent hepatitis in vulnerable hosts, unrecognized rodent exposure may become clinically relevant during diagnostic workups for unexplained hepatitis.

The study is also a reminder that urban zoonoses often move through infrastructure rather than dramatic animal encounters. Sewers, refuse channels, drainage systems, and crowded residential habitats can maintain contact chains that are invisible to patients and often to clinicians. In that setting, a virus with liver tropism and documented human infectivity deserves attention even when overt outbreaks are absent.

The remaining gap is transmission, not presence

Presence in rats is now well documented across French cities; direct proof of transmission pathways to humans is still thinner. The authors expanded the molecular evidence base with 20 full genomes, but the next clinical question is how often human infection follows local exposure, which activities carry the greatest risk, and whether specific urban microenvironments amplify transmission. Those answers will determine whether rHEV remains a niche zoonotic curiosity or becomes a more routine consideration in hepatitis diagnostics.

For now, the data support a straightforward conclusion: rHEV is enzootic in brown rats in French cities, and the combination of high prevalence, age-associated infection, and close genetic ties to human sequences makes the reservoir hard to ignore.


Reporting by Dr. A.R. Athira, MBBS for Medicine World Foundation, with additional data provided by CDC Emerging Infectious Diseases.