Mice are Not Susceptible to Hepatitis E Virus Infection

Abstract

ABSTRACT. To determine whether or not mice are susceptible to hepatitis E virus (HEV) infection, C57BL/6 mice were experimentally infected with genotypes 1, 3 and 4 HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA. The virus infection was monitored up to two months after inoculation; however, none of the serum or stool samples was positive for virus replication, demonstrating that C57BL/6 mice were not susceptible to HEV. KEY WORDS: C57BL/6, hepatitis E, hepatitis E virus, HEV, mouse.J. Vet. Med. Sci. 70(12): 1359-1362, 2008 Hepatitis E is a serious public health concern in many developing countries, and recognized as sporadic and endemic acute hepatitis in many industrialized countries. Pregnant women have a high risk associated with hepatitis E, with a high mortality rate (up to 20%) [5,25]. The causative agent of hepatitis E is hepatitis E virus (HEV), and this virus transmits primarily via the fecal-oral route through contaminated drinking water [1,6]. HEV is the sole member of the genus Hepevirus in the family Hepeviridae. HEV is a small round non-enveloped virus, 27-34 nm in diameter, containing an RNA genome approximately 7.2 kb in length [2,3]. The RNA consists of a single-strand RNA molecule containing three discontinuous and partially overlapping open reading frames (ORFs). The 3' terminus of the RNA is polyadenylated. HEV isolates were grouped into at least four major genotypes, genotypes 1, 2, 3 and 4 (G1, G2, G3 and G4) on the basis of nucleotide and deduced amino acid sequences [3,6,24]. Because G3 and G4 HEV were isolated from pigs and wild boars in addition to humans, and much direct and indirect evidence has indicated that HEV transmits from pigs or wild boars to humans, hepatitis E is recognized as a zoonotic disease [8,18,23]. Many studies have reported the detection of HEV RNA and the HEV-specific antigen (HEV-Ag) in pig and wild boar stool and serum specimens, and suggested the active circulation of this virus among these animals [18,20,26]. HEV-specific antibodies have been detected in many animals including sheep, cows, dogs, cats, wild rats, wild deer and mongoose, in addition to pigs and wild boars [9,12,14,15,19]. However, it is obscure whether or not HEV substantially replicates in these animals. In this study we infected C57BL/6 mice with G1, G3 and G4 HEV, and monitored the virus growth to determine the susceptibility of mice to HEV infection.G1 HEV strain was derived from stool specimens from a cynomolgus monkey (Macaca fascicularis), born and grown in the Tsukuba Primate Center for Medical Science, National Institute of Infectious Diseases (NIID), which had been experimentally infected with an Indian strain [10]. The G3 HEV strain (DQ079632) was derived from stool specimens collected on a pig farm in Japan. The G4 HEV strain (DQ079628) was from a stool specimen collected from a wild boar caught in Aichi prefecture, Japan. The stool specimens were used to prepare 10% (w/v) suspensions as descr...

Hepatitis E Virus Infection among Animals and Humans in Xinjiang, China: Possibility of Swine to Human Transmission of Sporadic Hepatitis E in an Endemic Area

“…Trials to experimentally infect laboratory rats or mice with human HEV led to contradictory results, because some studies reported successful infection and others did not. 27,28 Recently, an HEV-related agent was detected from wild rats, and sequence comparison to human and avian HEV strains revealed only 59.9% and 49.9% nucleotide identity, respectively. 29 The low nucleotide sequence identities between rat HEV and human HEV may indicate an independent evolution of both viruses with no transmission between both hosts.…”

Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR

“…Trials to infect laboratory rats or mice experimentally with human HEV led to contradictory results, as some studies reported successful infection whilst others did not (Karetnyï et al, 1993;Li et al, 2008;Maneerat et al, 1996). Several studies have shown the detection of HEV-specific antibodies in rodents from different countries including India, Vietnam, Brazil, Japan and the USA, including commensal rodents such as Norway (Rattus norvegicus) and black (Rattus rattus) rats, but also wild rodents such as deer mouse (Peromyscus maniculatus) and cotton rat (Sigmodon hispidus) (Arankalle et al, 2001;Favorov et al, 2000;Hirano et al, 2003;Kabrane-Lazizi et al, 1999;Meng et al, 2002;Vitral et al, 2005).…”

“…HEV-specific antibodies as well as viral RNA have been detected in several animal species (Smith, 2001;Meng, 2009 An initial indication for a potential role of rodents in the transmission of hepatitis E was found by the detection of HEV antigen in the sera of rodents caught next to a Russian village where an outbreak of hepatitis E was reported (Karetnyï et al, 1993). Trials to infect laboratory rats or mice experimentally with human HEV led to contradictory results, as some studies reported successful infection whilst others did not (Karetnyï et al, 1993;Li et al, 2008;Maneerat et al, 1996). Several studies have shown the detection of HEV-specific antibodies in rodents from different countries including India, Vietnam, Brazil, Japan and the USA, including commensal rodents such as Norway (Rattus norvegicus) and black (Rattus rattus) rats, but also wild rodents such as deer mouse (Peromyscus maniculatus) and cotton rat (Sigmodon hispidus) (Arankalle Favorov et al, 2000;Hirano et al, 2003;Kabrane-Lazizi et al, 1999; Meng et al, 2002;Vitral et al, 2005).…”

Characterization of Hepatitis E Virus Recombinant ORF2 Proteins Expressed by Vaccinia Viruses

“…However, antibody titers were lower and less lasting than those previously observed after vaccination with baculovirus-expressed proteins (18). Although HEV has recently been detected in rats with shedding of virus (21,23,37), and HEV experimental infection has been reported with nude mice (15), HEV does not seem to infect immunocompetent mice (26); therefore, the protective capacity of the immunological status acquired by these animals after vaccination with the recombinant vaccinia viruses was not evaluated.…”