RESUMO
Hepatitis E virus (HEV) has been detected in rabbits, but whether rabbit HEV strains can be transmitted to humans is not known. Of 919 HEV-infected patients in France during 2015-2016, five were infected with a rabbit HEV strain. None of the patients had direct contact with rabbits, suggesting foodborne or waterborne infections.
Assuntos
Vírus da Hepatite E/classificação , Vírus da Hepatite E/genética , Hepatite E/transmissão , Hepatite E/virologia , Zoonoses/transmissão , Zoonoses/virologia , Adulto , Animais , França/epidemiologia , Genótipo , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral , Coelhos , Zoonoses/diagnóstico , Zoonoses/epidemiologiaRESUMO
The recent discovery of hepatitis E virus (HEV) strains in rabbits in the People's Republic of China and the United States revealed that rabbits are another noteworthy reservoir of HEV. However, whether HEV from rabbits can infect humans is unclear. To study the zoonotic potential for and pathogenesis of rabbit HEV, we infected 2 cynomolgus macaques and 2 rabbits with an HEV strain from rabbits in China. Typical hepatitis developed in both monkeys; they exhibited elevated liver enzymes, viremia, virus shedding in fecal specimens, and seroconversion. Comparison of the complete genome sequence of HEV passed in the macaques with that of the inoculum showed 99.8% nucleotide identity. Rabbit HEV RNA (positive- and negative-stranded) was detectable in various tissues from the experimentally infected rabbits, indicating that extrahepatic replication may be common. Thus, HEV is transmissible from rabbits to cynomolgus macaques, which suggests that rabbits may be a new source of human HEV infection.
Assuntos
Reservatórios de Doenças/veterinária , Vírus da Hepatite E/fisiologia , Hepatite E/transmissão , Hepatite E/veterinária , Macaca fascicularis/virologia , Coelhos/virologia , Animais , Anticorpos Antivirais/sangue , Reservatórios de Doenças/virologia , Hepatite E/sangue , Hepatite E/virologia , Vírus da Hepatite E/isolamento & purificação , Humanos , Masculino , RNA Viral/sangue , RNA Viral/genética , Replicação ViralRESUMO
Rabbit hepatitis E virus (HEV) has been detected among rabbits and recently isolated from immunocompromised patients, suggesting zoonotic transmission. In this study, HEV infection among feral rabbits (Oryctolagus cuniculus) was assessed by detection of anti-HEV antibodies and HEV RNA. The prevalence of anti-HEV antibodies in sera was of 33 % (20/60) and HEV RNA was detected from only one of fecal swabs (1.7 %, 1/58). Furthermore, one naïve rabbit was intravenously inoculated with the suspension of the HEV-positive fecal specimen, exhibiting persistent HEV shedding in feces, intermittent viremia, seroconversion to anti-HEV IgM and IgG, and high alanine aminotransferase (ALT) values, indicating persistent HEV infection. The isolate JP-59 had a length of 7,282 bp excluding a poly (A) tail and possessed the characteristic 93 bp-insertion in ORF1. Phylogenetic analysis indicated that JP-59 formed a cluster with other rabbit HEV isolates from rabbits and human origin. The JP-59 shared the nucleotide sequence identities less than 87 % with other rabbit HEVs, suggesting that a novel rabbit HEV strain was circulating in Japan.
Assuntos
Vírus da Hepatite E , Hepatite E , Animais , Anticorpos Anti-Hepatite/sangue , Hepatite E/epidemiologia , Hepatite E/veterinária , Vírus da Hepatite E/classificação , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/isolamento & purificação , Japão/epidemiologia , Filogenia , RNA Viral/genética , CoelhosRESUMO
Rabbit hepatitis E virus (HEV) is a novel zoonotic infectious agent. Although a cell culture system to grow the virus has been established, there is currently no reverse genetics system for generating the virus. In this study, capped genomic rabbit HEV RNAs generated by in vitro transcription were transfected into PLC/PRF/5 cells, and the recovered viruses were subsequently passaged in the cells. The cell culture supernatant was capable of infecting rabbits negative for anti-HEV antibody by intravenous and oral inoculation, indicating that rabbit HEV generated by the reverse genetics system is infectious. Genome-wide analyses indicated that no nucleotide sequence change occurred in the virus genomes that were recovered from the cell culture supernatant after transfection and passaged one time or in the virus genomes recovered from faecal specimens of the infected rabbits. Ribavirin, a broad-spectrum anti-viral inhibitor, efficiently abrogated virus replication ex vivo and transiently suppressed the virus growth in the virus-infected rabbits, suggesting that this reagent is a candidate for therapeutic treatment. In addition, transmission of rabbit HEV to rabbits caused persistent infection, suggesting that the virus-infected rabbit could be an animal model for virus-induced hepatitis. The infectious rabbit HEV produced by a reverse genetics system would be useful to elucidate the mechanisms of HEV replication and the pathogenesis of viral hepatitis.