Abstract
Rat hepatitis E virus (rat HEV) was first identified in wild rats and was classified as the species Orthohepevirus C in the genera Orthohepevirus, which is genetically different from the genotypes HEV-1 to HEV-8, which are classified as the species Orthohepevirus A. Although recent reports suggest that rat HEV transmits to humans and causes hepatitis, the infectivity of rat HEV to non-human primates such as cynomolgus and rhesus monkeys remains controversial. To investigate whether rat HEV infects non-human primates, we inoculated one cynomolgus monkey and five rhesus monkeys with a V-105 strain of rat HEV via an intravenous injection. Although no significant elevation of alanine aminotransferase (ALT) was observed, rat HEV RNA was detected in fecal specimens, and seroconversion was observed in all six monkeys. The partial nucleotide sequences of the rat HEV recovered from the rat HEV-infected monkeys were identical to those of the V-105 strain, indicating that the infection was caused by the rat HEV. The rat HEV recovered from the cynomolgus and rhesus monkeys successfully infected both nude and Sprague-Dawley rats. The entire rat HEV genome recovered from nude rats was identical to that of the V-105 strain, suggesting that the rat HEV replicates in monkeys and infectious viruses were released into the fecal specimens. These results demonstrated that cynomolgus and rhesus monkeys are susceptible to rat HEV, and they indicate the possibility of a zoonotic infection of rat HEV. Cynomolgus and rhesus monkeys might be useful as animal models for vaccine development.
Highlights
Hepatitis E virus (HEV) is a non-enveloped positive-sense single-strand RNA virus, and it has been classified into the Hepeviridae family, which includes two genera—Orthohepevirus and Piscihepevirus [1]
A portion of the ORF1 genome was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using the fecal samples collected on days 15 to 19 p.i., and the nucleotide sequence analyses confirmed that 280 bp of ORF1 amplified from five fecal specimens were identical to those of the strain V-105 used for the inoculation
Human hepatitis E is caused mainly by HEV-1 to -4 and HEV-7, they all belong to the species HEV-A, and evidence of zoonotic infections of Rat hepatitis E virus (rat HEV) is increasing
Summary
Hepatitis E virus (HEV) is a non-enveloped positive-sense single-strand RNA virus, and it has been classified into the Hepeviridae family, which includes two genera—Orthohepevirus and Piscihepevirus [1]. The species HEV-A includes eight genotypes (HEV-1 to HEV-8). That have been identified in humans, monkeys, pigs, wild boars, deer, camels, mongooses, and rabbits [2,3]. The species HEV-C includes at least four genotypes (HEV-C1 to HEV-C4), and these were identified in rodents, ferrets, mink, kestrel, and foxes [4,5]. HEV-B and HEV-D were detected in birds and bats, respectively [1]. Hepatitis E in humans is caused mainly by HEV-1 to HEV-4 infection, some cases were reported to be caused by HEV-7 or rat HEV [6–8]. G5 and G8 HEV have the potential for zoonotic infection, since they are known to transmit to a non-human primate, i.e., the cynomolgus monkey [9–11]
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