If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global.
A total of 267 patients with acute hepatitis were divided into 2 cohorts, i.e. cohort 1 (without hepatotropic virus infection, n = 169) and 2 (with HEV infection, n = 98) to detect rat HEV (Orthohepevirus C; HEV-C1) RNA. A total of 2 individuals with mild acute hepatitis in cohort 1 and 1 individual (anti-HEV IgM positive) with severe acute hepatitis in cohort 2 were positive for HEV-C1 RNA. Although the first case of rat HEV-infected human was reported in a liver transplant recipient with chronic HEV infection in Hong Kong in 2018,
this study is the first to report HEV-C1 infection in Europe in acute HEV-infected patients. Rat HEV was previously thought to infect rodents and cannot infect humans exclusively. However, the HEV-C1 infection has emerged in Hong Kong,
indicating the possibility of transmission of rat HEV to humans. Rats, which closely and frequently come into contact with humans and domestic animals, have become a natural reservoir of HEV. Thus, the prevalence of HEV-C1 in these regions where HEV is highly prevalent in humans and domestic animals should be investigated.
A total of 68 wild rats (Rattus norvegicus, 31 females and 37 males) were collected for HEV-C1 detection in Dali City, Yunnan Province, Southwest China, where a high prevalence of genotype 4 HEV has been reported in humans, cows, and goats because of the traditional mixed farming of domestic animals.
Notably, 19.1% (13/68) liver, 19.1% (13/68) intestine, 16.2% (11/68) spleen, 10.3% (7/68) kidney, 16.1% (5/31) uterus, and 21.6% (8/37) testis samples were positive for HEV-C1 RNA by quantitative real-time PCR (Fig. 1A). The liver, which is the most important replication site of HEV, had the highest HEV-C1 titer (5.4×105 ± 4.1×105 copies/g, Fig. 1B). In addition, HEV antigens were observed in the liver, spleen, kidney, intestine, uterus, and testis on immunohistochemical assays in our previous study,
whereas no signal is noted in HEV-C1 RNA-negative mock rats (Fig. 1C). Both HEV-C1 RNA and HEV antigens positive were determined to be HEV-C1 infection. Considering that rat HEV has been identified to be infectious to non-human primates and BALB/c mice are susceptible to human- or swine-derived HEV, cross-species transmission is conceivable.
The Orthohepevirus A (HEV-A) infection causes a self-limited disease in immunocompetent individuals and chronicity in immunosuppressed patients. Up to now, 20 cases of HEV-C1-infected humans, including 16 in Hong Kong,
However, the clinical features of HEV-C1 infections are still largely unclear. Elevated ALT may be an important indicator in HEV-C1-infected patients, whereas no significant increase in ALT is observed in HEV-C1-infected rhesus and cynomolgus monkey models.
HEV-A, including 8 genotypes that infect humans, pigs, wild boar, cows, deer, rabbits, and camels, primarily causes human infection. The zoonotic transmission of HEV-A genotypes 3 and 4 from animals to humans by consumption of raw/undercooked pork or milk have been reported.
HEV-C1 was first identified in Rattus norvegicus from Germany in 2010, and it has been detected in Rattus rattus and Rattus norvegicus in the USA, China, Indonesia, Vietnam, and many European countries.
Consistently, we detect HEV-C1 RNA in the Rattus norvegicus captured from the farmers’ house, where humans, swine, cows, goats, and dogs live together, aggravating the possibility of cross-species transmission. The high prevalence of HEV-C1 in rats in Dali City may be associated with the high prevalence of HEV-A in humans and domestic animals. The lessons from SARS and COVID-19 remind us to keep alert to zoonotic diseases. Therefore, HEV-C1 investigation should be performed in the future in these regions, where HEV-A is prevalent, to assess the potential risk of HEV-C1 to humans. However, the absence of sensitive and commercial HEV-C1 detection kits may hamper such investigations.
In summary, rat HEV can be transmitted across species to humans. The high prevalence of HEV-C1 in these traditional mixed farming regions will aggravate the zoonotic transmission of HEV.
This study was supported by Natural Science Foundation for Distinguished Young Scholars of Yunnan Province ( 202001AV070005 ), Program for Innovative Research Team (in Science and Technology) in University of Yunnan Province (2020), Yunnan Provincal Key Laboratory of Clinical Virology ( 202205AG070053 ), CAMS Innovation Fund for Medical Sciences ( 2021-I2M-1-024 ), Scientific and Technological Innovation Talents of Yunnan Province ( 202205AD160008 ) and Program for Cultivating Reserve Talents in Medical Disciplines from the Health Committee of Yunnan Province ( H-2019043 ).
Z. Q and X. H participated in the data acquisition, analysis, and interpretation and drafted the initial manuscript. Y. X participated in the acquisition of the data. W. Y collected the samples and provided technical and financial support. F. H was the guarantor and designed the study.
Conflict of interest
The authors declare no conflicts of interest that pertain to this work.
Please refer to the accompanying ICMJE disclosure forms for further details.
We thank Huchun Peng and local farmers for their collection of rats.
The following are the supplementary data to this article: