Review of Hepatitis E Virus in Rats: Evident Risk of Species Orthohepevirus C to Human Zoonotic Infection and Disease

Abstract

Hepatitis E virus (HEV) (family Hepeviridae) is one of the most common human pathogens, causing acute hepatitis and an increasingly recognized etiological agent in chronic hepatitis and extrahepatic manifestations. Recent studies reported that not only are the classical members of the species Orthohepevirus A (HEV-A) pathogenic to humans but a genetically highly divergent rat origin hepevirus (HEV-C1) in species Orthohepevirus C (HEV-C) is also able to cause zoonotic infection and symptomatic disease (hepatitis) in humans. This review summarizes the current knowledge of hepeviruses in rodents with special focus of rat origin HEV-C1. Cross-species transmission and genetic diversity of HEV-C1 and confirmation of HEV-C1 infections and symptomatic disease in humans re-opened the long-lasting and full of surprises story of HEV in human. This novel knowledge has a consequence to the epidemiology, clinical aspects, laboratory diagnosis, and prevention of HEV infection in humans.

Rats in the city: implications for zoonotic disease risk in an urbanizing world

“…Notably, the prevalence of all viruses detected in this study was low. However, SERV, WENV, and HEV-C1 are known zoonotic pathogens, while the Embecovirus subgenus of betacoronaviruses contains several viruses capable of infecting people, including HCoV-OC43 and HCoV-HKU1 (Pattamadilok et al 2006, Jonsson et al 2010, Gamage et al 2011, Decaro & Lorusso 2020, Reuter et al 2020).…”

“…HEV-C1 was predominantly identified from R. rattus lineage R3 (86% of detections) at sites with high rodent density, a high proportion of built infrastructure, and substantial resource provisioning from adjacent markets and restaurants. HEV-C1 has previously been detected in a wide range of rodent species across three continents (Asia, Europe, North America), and occasional spillovers into other mammals, including people, have been documented (Andonov et al 2019, Pallerla et al 2020, Reuter et al 2020, Sridhar et al 2018, 2020). Globally, zoonotic transmission of HEV-C1 through contact with rodent feces appears infrequent.…”

“…Globally, zoonotic transmission of HEV-C1 through contact with rodent feces appears infrequent. However, there is a paucity of data as commercially available tests for HEV are designed to detect Orthohepevirus A (human HEV) only, and these have failed to detect clinical HEV-C1 infections in the past (Sridhar et al 2018, 2020, Andonov et al 2019, Reuter et al 2020). Similarly, although a growing number of rodent-borne paramyxoviruses have been sequenced in the past decade, little is known about the zoonotic potential of these viruses.…”

“…only, and these have failed to detect clinical HEV-C1 infections in the past (Sridhar et al 2018, Andonov et al 2019, Reuter et al 2020. Similarly, although a growing number of rodentborne paramyxoviruses have been sequenced in the past decade, little is known about the zoonotic potential of these viruses.…”

Advances in Hepatitis E Virus Biology and Pathogenesis

“…A rat HEV strain of Orthohepevirus C was found in a patient with persistent hepatitis after liver transplantation, suggesting the zoonotic potential of this species [ 25 ]. The genomic variability and potential risk of cross-species infection of Orthohepevirus C strains have been reviewed elsewhere [ 26 , 27 ]. Along with the isolation of HEV from more wild and domestic animals, an evolution of the virus taxonomy is expected in the future.…”