Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/35280
Title: Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis)
Authors: Mejido, Diana Chaves Pereira
Oliveira, Jaqueline Mendes de
Gaspar, Ana Maria Coimbra
Gardinali, Noemi Rovaris
Bottino, Fernanda de Oliveira
Carvalho, Lilian Gonçalves de
Santos, Debora Regina Lopes dos
Kevorkian, Yohan Brito
Xavier, Leandro Layter
Moran, Julio
Pelajo-Machado, Marcelo
Marchevsky, Renato Sergio
Pinto, Marcelo Alves
Affilliation: 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.
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.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Ciência e Tecnologia de Biomodelos. Rio de Janeiro, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro. Departamento de Microbiologia Veterinária e Imunologia. Seropédica, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Instituto de Biologia. Laboratório de Morfometria. Rio de Janeiro, RJ, Brasil / Grupo de Trabalho de Recursos Humanos em Biotecnologia do GECIV. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Dr Julio Moran Laboratories. Ebmatigen, Zurich, Switzerland.
Fundação Oswaldo Cruz. Biomanguinhos. Laboratório de Controle de Neurovirulência. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Abstract: Hepatitis E virus genotype 3 (HEV-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis E worldwide. Primate models have proven to be an essential tool for the study of HEV pathogenesis. Here we describe the outcomes of HEV infection in Macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. Eight adult cynomolgus macaques were inoculated intravenously with HEV-3 viral particles isolated from swine and human samples. Liver, spleen, duodenum, gallbladder and bile were sequential assessed up to the end-point of this study, 67 days post-inoculation (dpi). Our previously published findings showed that biochemical parameters return gradually to baseline levels at 55 dpi, whereas anti-HEV IgM and HEV RNA become undetectable in the serum and feces of all animals, indicating a non-viremic phase of recovery. Nevertheless, at a later stage during convalescence (67 dpi), the presence of HEV-3 RNA and antigen persist in central organs, even after peripheral viral clearance. Our results show that two cynomolgus inoculated with swine HEV-3 (animals I3 and O1) presented persistence of HEV RNA low titers in liver, gallbladder and bile. At this same stage of infection, HEV antigen (HEV Ag) could be detected in all infected animals, predominantly in non-reactive Kupffer cells (CD68+iNOS-) and sinusoidal lining cells. Simultaneously, CD4+, CD3+CD4+, and CD3+CD8+ immune cells were identified in hepatic sinusoids and small inflammatory clusters of lobular mononuclear cells, at the end-point of this study. Inability of HEV clearance in humans can result in chronic hepatitis, liver cirrhosis, with subsequent liver failure requiring transplantation. The results of our study support the persistence of HEV-3 during convalescence at 67 dpi, with active immune response in NHP. We alert to the inherent risk of viral transmission through liver transplantation, even in the absence of clinical and biochemical signs of acute infection. Thus, besides checking conventional serological markers of HEV infection, we strongly recommend HEV-3 RNA and antigen detection in liver explants as public health measure to prevent donor-recipient transmission and spread of hepatitis E.
Keywords: Hepatitis E virus
Genotype 3
Cynomolgus monkeys
Liver parenchyma
Persistence and reactivity
keywords: Vírus da Hepatite E
Genótipo 3
Macacos cinomolgos
Parênquima hepático
Persistência e reatividade
Issue Date: 2019
Publisher: Public Library of Science
Citation: MEJIDO, Diana Chaves Pereira et al. Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis). Plos One, v. 14, n. 6, p. 1-18, June 2019.
DOI: 10.1371/journal.pone.0218472
ISSN: 1932-6203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos
ICTB - Artigos de Periódicos
Biomanguinhos - Artigos de Periódicos
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