Hepatitis E virus infection in chimpanzees: a retrospective analysis

McCaustland, Karen A.; Krawczyński, K.; Ebert, James W.; Balayan, M. S.; Andjaparidze, A. G.; Spelbring, John; Cook, E. H.; Humphrey, Charles D.; Yarbough, Patrice O.; Favorov, Michael O.; Carson, D.; Bradley, Daniel W.; Robertson, Betty H.

doi:10.1007/s007050070065

Cited by 45 publications

(30 citation statements)

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“…The same frozen fecal suspension was used as the intravenous inocula for the shedder pigs in the current and previous experiments (13,17,18). The freeze-thaw process might have affected the ratio of infectious to defective HEV particles (4,23) and contributed to the unsuccessful transmission of the HEV via the oral route in a previous experiment (17).…”

Section: Discussionmentioning

confidence: 99%

Routes of Transmission of Swine Hepatitis E Virus in Pigs

et al. 2004

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Hepatitis E virus (HEV) is believed to be transmitted by the fecal-oral route in pigs. To date, in experiments, HEV has been transmitted successfully only by the intravenous or intrahepatic route. To assess the route of HEV transmission, 27 pigs were separated into nine groups of three pigs. Positive-control pigs were inoculated intravenously with swine HEV and served as the source of HEV for the other groups. Uninoculated contact pigs were placed in the positive-control group. On three consecutive days, naïve pigs were inoculated using samples collected from the positive-control pigs at 9, 10, and 11 days postinoculation. The tonsils and nasal mucosa of each positive-control pig were swabbed and that swab was used to rub the tonsils and nasal and ocular mucosa of naïve pigs. The positive-control pigs were also injected with bacterin, and the same needle was used to immediately inject naïve pigs. Feces were collected from positive controls and fed by oral gavage to naïve pigs. Weekly fecal and serum samples from each pig were tested for anti-HEV antibodies and HEV RNA. All positive-control pigs shed the virus in feces; two pigs were viremic and seroconverted to anti-HEV. All contact control pigs shed the virus in feces; two seroconverted and one became viremic. One of three pigs in the fecal-oral exposure group shed the virus in feces and seroconverted. Pigs exposed to the contaminated needles or the tonsil and nasal secretion swabs remained negative. This is the first report of experimental fecal-oral transmission of HEV in swine.

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Section: Discussionmentioning

confidence: 99%

Routes of Transmission of Swine Hepatitis E Virus in Pigs

et al. 2004

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“…Direct and indirect evidence of HEV transmission from wild boars and pigs to humans has been reported in Japan, suggesting that these animals are the main zoonotic reservoirs in this country [8,27]. Chimpanzees, rhesus monkeys, cynomolgus monkeys, and marmosets have been used for experimental infection and to evaluate the efficacy of HEV vaccines, and HEV has been used as a challenge virus, indicating that these monkeys are susceptible to HEV infection [13,22,29,30]. In addition to these animals, anti-HEV IgG antibody has been detected in dogs, cats, cows, goats, sheep, and rodents including rats [4,7,14,19], and anti-HEV IgG antibody and HEV RNA were detected from mongoose and wild deer [9,21,28].…”

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confidence: 99%

Mice are Not Susceptible to Hepatitis E Virus Infection

Suzaki

Ami

et al. 2008

The Journal of Veterinary Medical Science

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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...

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“…Este perfil foi previamente observado em chimpanzés inoculados com suspensões fecais dos genótipos 1 (MCCAUSTLAND et al, 2000) e 3 suíno (MENG et al, 1998b) e em macacos cynomolgus infectados por pool de soro e fezes humana do genótipo 3 (CARVALHO et al, 2013). Os chimpanzés e o cynomolgus não apresentaram sinais clínicos ou aumento significantes nos níveis de transaminases, assim como o animal AH-06/10 que, exceto por dois eventos de diarreia observados nas semanas 1 e 2, não apresentou outras alterações clínicas ou distúrbios bioquímicos séricos.…”

Section: Etapa 2 -Estudo Experimental De Infecção Por Genótipo 3 Suínunclassified

“…Estes perfis de detecção do HEV-RNA somente no soro ou fezes pode ter relação com a dose do inóculo (TSAREV et al, 1992;1994a;MENG et al, 1998b;MCCAUSTLAND et al, 2000), tempo de armazenamento da amostra e/ou redução da infectividade do inóculo (CARVALHO et al, 2013;MCCAUSTLAND et al, 2000).…”

Section: Etapa 2 -Estudo Experimental De Infecção Por Genótipo 3 Suínunclassified

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<b>Detecção e quantificação do vírus da hepatite E (HEV) por RT-PCR em tempo real e estudo experimental em primatas neotropicais (<i>Aotus azarai infulatus</i>) infectados pelo genótipo 3 do HEV</b>

Souza¹

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Detecção e quantificação do vírus da hepatite E (HEV) por RT-PCR em tempo real e estudo experimental em primatas neotropicais (Aotus AGRADECIMENTOSÀ minha família, em especial aos meus pais Francisco e Ana Maria (in memorian), minha irmã Alessandra "Alê", minha avó Raimunda, "mãe mundica", minha tia Ana Cristina, "Cris" e minha afilhada Júlia, "Juju". Peço desculpas pelas inúmeras circunstâncias em que precisei estar ausente/longe/ocupado, mas queria registrar de todo coração o meu profundo agradecimento a todos. Sem o apoio e incentivo de vocês, eu certamente não teria concluído mais essa etapa. Amo muito vocês, saibam que vocês são meu porto-seguro e minha maior motivação para ser um profissional e ser humano melhor.À professora e amiga Lílian Rose Marques de Sá. A minha "cara-de-pau" e sua boavontade fizeram com que você aceitasse a orientação sem nem mesmo me conhecer e hoje, quatro anos após "os macacos" terem unido nossas linhas de pesquisa, tenho certeza absoluta que não poderia ter feito escolha melhor de orientadora! Obrigado por ter aceitado esse desafio de orientar um projeto conduzido a uma distância continental e, consequentemente, pelos inúmeros votos de confiança depositados no meu trabalho e nos colegas do InstitutoEvandro Chagas e Centro Nacional de Primatas durante o desenvolvimento não só deste, mas também dos nossos outros projetos. Seu apoio e incentivo nos momentos de calmaria e, principalmente, naqueles períodos mais difíceis e desafiadores, foram fundamentais para que chegássemos aqui. Sinto-me muito honrado e feliz por levar "na bagagem" deste doutorado inúmeros aprendizados técnicos e científicos, que em grande parte vieram da sua admirável competência, e, além disso, por levar comigo o exemplo da sua inspiradora dedicação e amor pela Medicina Veterinária, pela ciência e vida acadêmica! Espero poder contar com sua parceria de trabalho e amizade por longos anos. Muito obrigado. O vírus da hepatite E (HEV) é um patógeno emergente de distribuição global, causador de hepatite aguda e crônica em humanos e infecções assintomáticas em animais. No Brasil a prevalência de infecção por HEV em humanos e animais ainda é pouco compreendida, assim como as características de virulência, patogenicidade e de infecção inter-espécies de isolados do genótipo 3, zoonótico, circulantes no país também são desconhecidas. O estudo foi dividido em duas etapas, com os objetivos de 1) contribuir no diagnóstico laboratorial molecular do HEV a partir do desenvolvimento de um protocolo de RT-PCR em tempo real (RT-qPCR) para pesquisa do HEV em amostras biológicas, e 2) contribuir com a compreensão das características moleculares, sorológicas, clínico-laboratoriais, ultrassonográficas e histopatológicas associadas à infecção experimental em macacos-da-noite (Aotus azarai infulatus) por um isolado do genótipo 3 suíno do HEV previamente detectado na Amazônia oriental brasileira. O protocolo de RT-qPCR foi desenvolvido com a caracterização da curva de detecção e aplicado em concomitância com testes sorológicos para avalia...

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Hepatitis E virus infection in chimpanzees: a retrospective analysis

Cited by 45 publications

References 17 publications

Routes of Transmission of Swine Hepatitis E Virus in Pigs

Routes of Transmission of Swine Hepatitis E Virus in Pigs

Mice are Not Susceptible to Hepatitis E Virus Infection

<b>Detecção e quantificação do vírus da hepatite E (HEV) por RT-PCR em tempo real e estudo experimental em primatas neotropicais (<i>Aotus azarai infulatus</i>) infectados pelo genótipo 3 do HEV</b>

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