A Cross-Species Transmission of a Camel-Derived Genotype 8 Hepatitis E Virus to Rabbits.

Wenjing Zhang,Masamichi Muramatsu,Yasushi Ami,Yuriko Suzaki,Tiancheng Li,Naokazu Takeda,Michiyo Kataoka

doi:10.3390/pathogens10111374

Wenjing Zhang, Masamichi Muramatsu + Show 5 more

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https://doi.org/10.3390/pathogens10111374

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Abstract

Novel genotypes of hepatitis E virus (HEV), i.e., HEV-5, HEV-7, and HEV-8, have been identified in wild boar, dromedary camels, and Bactrian camels, respectively, and they transmit to cynomolgus monkeys in a trans-species manner, raising the potential for zoonotic infection. Rabbits are the natural reservoir for rabbit HEV, but they are also susceptible to HEV-3 and HEV-4. It has been unknown whether rabbits are susceptible to HEV-5, HEV-7, and HEV-8. To investigate the infectivity of novel HEVs in rabbits and to assess whether rabbits are appropriate animal models for these HEVs, we inoculated Japanese white rabbits with HEV-5, HEV-7, and HEV-8, respectively. We observed that viral RNA was present in the fecal specimens of the HEV-8-inoculated rabbits and anti-HEV IgG antibodies were present in its sera, although anti-HEV IgM was undetectable and no significant elevation of ALT was observed. These results indicated that HEV-8 crossed species and infected the rabbits. No evidence for replication was observed in HEV-5 and HEV-7, suggesting that rabbits are not susceptible to these genotypes. The antibodies elicited in the HEV-8-infected rabbits did not protect them from the rabbit HEV challenge, suggesting that the antigenicity differs between HEV-8 and rabbit HEV. Antigenic analyses demonstrated that anti-HEV-8 antibodies reacted more strongly with homologous HEV-8 virus-like particles (VLPs) compared to heterologous rabbit HEV VLPs, but anti-rabbit HEV antibody had similar reactivity to the VLPs of rabbit HEV and HEV-8, suggesting that HEV-8 lacks some epitope(s) that exist in rabbit HEV and induced the neutralizing antibodies against rabbit HEV.

Highlights

Hepatitis E virus (HEV) is a causative agent of acute and chronic hepatitis E in humans and is distributed worldwide [1,2]
In cwoenrteraisdt,etnhteicvaliratol RtNhoAsewoafs cthoentiHnEuVal‐l8y duesteedctefodrutnhteil inoculat day 56 in rabbit G8Rb-1 (Figure 3a).uTnodecotencfitarmbletheininftehcetiosnerbay rcaoblbleicttHedEVf,rwome amthpelsifieedraabbits du Pathogens 2021, 10, x FOR PEER REVIpEoWrtion of the viral RNA genome beyxpReTr-iPmCeRntu. sing fecal samples collected on day 217 opf.1i.2, and the nucleotide sequence analyses confirmed that the 412 bp of ORF2 were identical to those of the rabbit HEV used for the inoculation
Infectivity of the HEVs was examined by an intravenous inoculation with the viruses recovered from the cell culture supernatants, more experiments are necessary to confirm whether natural HEV-5, HEV7, and HEV-8 strains can be transmitted to rabbits by oral inoculation

Summary

Introduction

Hepatitis E virus (HEV) is a causative agent of acute and chronic hepatitis E in humans and is distributed worldwide [1,2]. The genus Orthohepevirus includes at least four species: Orthohepeviruses A to D [3]. The species Orthohepevirus A includes eight genotypes designated genotypes 1 to 8 (HEV-1 to HEV-8) [3,4,5]. Most cases of hepatitis E have been caused by HEV-1 to HEV-4, novel HEVs including HEV-5, HEV-7, and HEV-8 are known to cross-transmit to non-human primates such as cynomolgus monkeys, raising a potential risk of zoonotic infection [6,7,8,9]. A human case of hepatitis E due to HEV-7 infection was reported in 2016 [10]

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