Detection of hepatitis E virus RNA in rats caught in pig farms from Northern Italy

Abstract

Hepatitis E virus (HEV) strains belonging to the Orthohepevirus genus are divided into four species (A–D). HEV strains included in the Orthohepevirus A species infect humans and several other mammals. Among them, the HEV‐3 and HEV‐4 genotypes are zoonotic and infect both humans and animals, of which, pigs and wild boar are the main reservoirs. Viruses belonging to the Orthohepevirus C species (HEV‐C) have been considered to infect rats of different species and carnivores. Recently, two studies reported the detection of HEV‐C1 (rat HEV) RNA in immunocompromised and immunocompetent patients, suggesting a possible transmission of rat HEV to humans. The role of rats and mice as reservoir of HEV and the potential zoonotic transmission is still poorly known and deserves further investigation. To this purpose, in this study, the presence of HEV RNA was investigated in the intestinal contents and liver samples from 47 Black rats (Rattus rattus) and 21 House mice (Mus musculus) captured in four pig farms in Northern Italy. The presence of both Orthohepevirus A and C was investigated by the real‐rime RT‐PCR specific for HEV‐1 to HEV‐4 genotypes of Orthohepevirus A species and by a broad spectrum hemi‐nested RT‐PCR capable of detecting different HEV species including rat HEV. The intestinal content from two Black rats resulted positive for HEV‐C1 RNA and for HEV‐3 RNA, respectively. None of the House mice was HEV RNA positive. Sequence analyses confirmed the detection of HEV‐C1, genotype G1 and HEV‐3 subtype e. The viral strain HEV‐3e detected in the rat was identical to swine HEV strains detected in the same farm. Liver samples were negative for the detection of either rat HEV or HEV‐3.

Infection dynamics and persistence of hepatitis E virus on pig farms – a review

“…From fifteen states in the USA though, all HEV sequences from the 35 rat livers positive, were related to HEV-3a [90]. Rats and mice trapped around pig farms were positive for HEV-3 in spleens in one study, but are mostly only positive in their intestines [47,86,89] or found test negative for HEV-3 [88]. The low prevalence of HEV-3 in rodents around farms and detection of HEV-3 predominantly in intestines, supports the argument that rodents are only accidental hosts of HEV-3.…”

“…In rats, HEV-3 RNA has been found, as well as a novel HEV gt, first called 'rat HEV' and now known as HEV gt C1 (species Orthohepevirus C) [87]. The prevalence of both HEV gt's in rodents varies from 0 to 18% dependent on the species (mice, R. rattus or R. norvegicus rats), the location where the rodents are found and the type of samples collected [47,86,[88][89][90][91]. In a study with 63 rats from twelve European countries, all contained HEV gt C1 RNA in their livers [91].…”

Orthohepevirus C: An Expanding Species of Emerging Hepatitis E Virus Variants

“…To date, the vast majority of Orthohepevirus C genomes have been identified in Norway rats, from countries including the USA, China, Germany, France, Denmark, Lithuania, England, Hungary, Austria, Switzerland, Italy, Spain, Greece, Belgium, the Czech Republic, and Vietnam, with all viral strains belonging to HEV-C1 [19,20,24,25,29,[36][37][38][39][40][41][42][43][44][45][46]. Orthohepevirus C genomes have been detected in numerous other members of the family Muridae: HEV-C1 from Rattus rattus (Black Rat) has been detected in Indonesia, China, Kenya, and 12 other European countries comprising Lithuania, Germany, Hungary, Denmark, Austria, Switzerland, France, Italy, Spain, Greece, Belgium, and the Czech Republic [29,30,32,41,47,48]; Rattus tanezumi (Oriental house rat) in Vietnam and China have also been reported to harbor the virus [26,36,44,49]; in China, HEV-C1 RNA has been detected in Rattus losea (Losea rat), Rattus flavipectus (Yellow-breasted rat), and Bandicota indica (Greater bandicoot rat) [25,43,44]; Apodemus chevrieri (Chevrier's field mouse) and Apodemus agrarius (Striped field mouse) were positive for Orthohepevirus C detection; however, these variants are phylogenetically divergent from known HEV-C1 or HEV-C2, and thus, cannot yet be classified [36,50].…”

Rat Hepatitis E Virus: Presence in Humans in South-Western France?

“…This rat HEV is a genetically distant relative of other mammalian HEVs; it is about 55-60% sequence homologous to HEV genotypes 1-4, and is assigned to the genus Orthohepevirus C (7). In Europe, studies conducted on Norway rats and Black rats, reported the detection of HEV-C RNA with prevalence ranging between 0.3 and 27.2% (8)(9)(10)(11)(12)(13)(14)(15); HEV-C RNA was also frequently detected in Asia with prevalence ranging between 0.7 and 26.3% in rats (16-21), 1.9% in musk shrew (22) and between 1.5 and 7.8% in 2 US studies in rats (23,24). The virus isolated in musk shrew could infect nude mice (25).…”