Spillover of rat hepatitis E virus into humans: an emerging zoonosis?

<i>Rocahepevirus ratti</i> (rat HEV) has become a zoonotic pathogen of growing public health concern. First identified in 2010 in wild rats in Germany, <i>Rocahepevirus ratti</i>-C1 (HEV-C1) was genetically distinct from <i>Paslahepevirus</i> genotypes that cause hepatitis E in humans. Although early research indicated that HEV-C1 could not infect non-human primates, reports of human infections in Hong Kong circa 2018 raised the possibility of a new zoonoses. Currently, 34 known human instances of rat HEV infection have been reported, affecting both immunocompetent and immunocompromised individuals. A critical review of the current knowledge regarding rat HEV, including its epidemiology, zoonotic spillover, health implications, and knowledge gaps with future research directions is presented in this paper. Here we describe possible modes of transmission, human pathophysiology, and clinical signs and symptoms in infected people. The need for diagnostic tools specific for rat HEV, current detection limitations, and diagnostic challenges are also discussed. We explore potential implications for public health, stressing the value of rodent control, surveillance, and preventive measures. Knowledge gaps in the field of rat HEV research are highlighted and future lines of inquiry to reduce the potential risks to public health posed by this emerging zoonotic virus are discussed.