Hepatitis E Virus in Rats, Los Angeles, California, USA

Abstract

The role of rats in human hepatitis E virus (HEV) infections remains controversial. A genetically distinct HEV was recently isolated from rats in Germany, and its genome was sequenced. We have isolated a genetically similar HEV from urban rats in Los Angeles, California, USA, and characterized its ability to infect laboratory rats and nonhuman primates. Two strains of HEV were isolated from serum samples of 134 wild rats that had a seroprevalence of antibodies against HEV of ≈80%. Virus was transmissible to seronegative Sprague-Dawley rats, but transmission was spotty and magnitude and duration of infection were not robust. Viremia was higher in nude rats. Serologic analysis and reverse transcription PCR were comparably sensitive in detecting infection. The sequence of the Los Angeles virus was virtually identical to that of isolates from Germany. Rat HEV was not transmissible to rhesus monkeys, suggesting that it is not a source of human infection.H epatitis E virus (HEV) is a major cause of epidemic waterborne and sporadic hepatitis in developing countries. Hepatitis E is caused principally by HEV genotypes 1 and 2 (1). Recently, hepatitis E has been diagnosed with increasing frequency as a cause of sporadic hepatitis in industrialized countries (2). Additionally, a large proportion (<20%) of populations of such countries have antibodies against HEV in the absence of any recognized hepatitis (3-5), and evidence is increasing that these antibodies might be the result of subclinical infections acquired zoonotically.Strains of HEV representing genotypes 3 and 4, which have been isolated from humans with hepatitis E, regularly infect pigs worldwide (6), and infection in humans caused by eating undercooked meat from domestic pigs, wild boar, and several species of wild deer has been documented (6,7). However, many, if not most, persons who have unexplained antibodies against HEV do not eat undercooked pork or venison, raising the possibility that other animals or modes of zoonotic transmission exist. It is noteworthy that swine handlers in the United States have a higher incidence of antibodies against HEV than do healthy blood donors, even though pork is generally thoroughly cooked in the United States. Therefore, eating pork is unlikely to explain the prevalence of antibodies against HEV in this country.Numerous species, including rodents, have been found to have antibodies reactive with capsid protein of human HEV strains, and HEV closely related to genotypes 3 or 4 has been recently isolated from rabbits (8), cattle (9), and sheep (10). However, an HEV strain recently isolated from rats was unique and only distantly related to known strains (11). Thus, it is important to understand how this rat virus is related to human infections. Rats are particularly interesting as a potential source of human infections because although they are not a human food, they have a high seroprevalence of antibodies against HEV (12,13) and they are ubiquitous and in close contact with humans everywhere.We have demonstrated that a hi...

Host Immune Status and Response to Hepatitis E Virus Infection

“…The known animal reservoirs of HEV continue to multiply; novel members of the Hepeviridae have been detected in wild and farmed rabbits, wild rats, birds, bats, and trout (13,15,(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106). Of these, only rabbit HEV strains have been shown to share a close phylogenetic relationship and possess antigenic similarity to human-and swine-associated HEV strains.…”

Construction and characterization of an infectious cDNA clone of rat hepatitis E virus

“…Experimentally infected Wistar rats showed transient virus shedding and developed anti-rat HEV-specific antibodies (Li et al, 2013b). Clinical signs were not recorded after experimental infection of rats (Li et al, 2013b;Purcell et al, 2011). Preliminary infection trials with rat-derived cell cultures did not result in rat HEV replication (Johne et al, 2010a).…”

Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

“…The proteins encoded by ORF2 and ORF3 are produced from a bicistronic subgenomic (SG) mRNA, and the coding region of ORF2 overlaps ORF3, but neither overlaps ORF1 (8,9). To date, complete genomes of many animal HEVs, including HEVs from pigs (10), chickens (11,12), rabbits (13), deer (14), mongooses (15), rats (16,17), bats (18), and ferrets (19), have been characterized, and the host range and molecular diversity of HEVs are continually expanding (20). Swine HEV, the first identified animal strain of HEV, shares 80% to 90% nucleotide sequence identity with human HEV and can infect nonhuman primates (10).…”