Rat hepatitis E virus (HEVrat), classified as genotype 1 of Rocahepevirus ratti, is known to be widely circulating in rodent populations. In 2017, researchers first identified HEVrat as a causative agent of hepatitis in humans, confirming its zoonotic potential and drawing considerable attention. As of May 2025, a total of 43 human cases of HEVrat infection have been reported across Asia and Europe, indicating that such spillover events are neither rare nor isolated. One of the main challenges lies in the ~55% sequence identity between the capsid protein of HEVrat and that of Paslahepevirus balayani (HEVb), the major HEV species responsible for human hepatitis E. This sequence divergence results in heterogeneous and partly cross-reactive serological responses in individuals previously exposed to HEVrat and HEVb.
A recent study led by Prof. Ningshao Xia and Prof. Zizheng Zheng from Xiamen University, Assoc. Prof. Yihan Lu from Fudan University, and Assis. Prof. Lin Wang from Peking University, revealed potential zoonotic spillover burden of rat HEV to humans. The team developed a serological assay based on an antigen-competition principle, termed Distinguishing Antibody Response Elicitation (DARE). This approach utilizes magnetic beads conjugated with the capsid proteins of the two respective viruses, and quantifies the relative history of exposure by measuring serum IgG binding competition against immobilized capsid antigens on the assay plate. Using sera from mice immunized with viral capsid antigens and from infected gerbils, the researchers established a preliminary standardization pipeline and defined interpretable thresholds for assessing past viral exposure (Figure).
This study suggests that post-exposure to HEVrat may be substantially more common than previously recognized in some regions of China. Although no significant hepatitis-related disease burden appears to be associated with HEVrat at this stage, its zoonotic potential warrants continued surveillance and investigation. Meanwhile, the findings reaffirm that the hepatitis E disease burden in China remains predominantly driven by HEVb. The overall pathogenic risk of HEVrat calls for dynamic, long-term monitoring to proactively mitigate potential emerging public health threats.
Read the full article: Nature communications 2025 Apr 29;16(1):4038. DOI: 10.1038/s41467-025-59345-6
