Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30440
Title: Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication
Authors: Amado, Luciane A.
Marchevsky, Renato S.
Paula, Vanessa S. de
Hooper, Cleber
Freire, Marcos da S.
Gaspar, Ana Maria C.
Pinto, Marcelo A.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Biomanguinhos. Laboratório de Neurovirulência. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Serviço de Controle de Qualidade Animal. CECAL. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Biomanguinhos. Laboratório de Tecnologia Viral. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Abstract: This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (105 copies⁄ml), followed by serum viral load of 104 copies⁄ml at 20 dpi and saliva viral load of 103 copies⁄ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 · 104 copies⁄mg), salivary glands (1.9 · 103 copies⁄mg), tonsils (4.2 · 101 copies⁄mg) and lymph nodes (3.4 · 101 copies⁄mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection.
Keywords: cynomolgus
extrahepatic site
Hepatitis A
intermediate replicative
saliva and pathogenesis
keywords: local extra-hepático
replicativo intermediário
Hepatite A
saliva e patogênese
Macaca fascicularis
Issue Date: 2010
Publisher: Wiley
Citation: AMADO, Luciane A. et al. Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys ( Macaca fasciculari s ): evidence of active extrahepatic site of HAV replication. Int. J. Exp. Path., v. 91, p.87–97, 2010.
DOI: 10.1111/j.1365-2613.2009.00699.x
ISSN: 0959-9673
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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