Inducible nitric oxide synthase (iNOS) expression in liver and splenic T lymphocyte rise are associated with liver histological damage during experimental hepatitis A virus (HAV) infection in Callithrix jacchus

Pinto, Marcelo Alves; Marchevsky, Renato Sérgio; Pelajo-Machado, Marcelo; Santiago, Marta A; Pissurno, J.W.; França, Monique; Baptista, Márcia L.; Gouvêa, Aline Silva; Santana, A.A.; Bertho, Álvaro Luiz; Schatzmayr, H. G.; Gaspar, Ana; Kubelka, Claire Fernandes

doi:10.1016/s0940-2993(00)80006-8

Cited by 15 publications

(5 citation statements)

References 40 publications

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“…Controversially, we failed to detect double CD68+iNOS+ labeled cells and HEV+iNOS+. CD68+iNOS+ labeled cells was previously described by our group in NHP experimentally infected with hepatitis A virus [27]. Results of our present study reinforce the hypothesis of macrophage/monocyte deactivation by HEV ORF3 system by inhibiting various PRRs-mediated NF-κB, thus signaling proinflammatory pathways [28][29] including IFN-γ production, which is essential for controlling HEV replication [30].…”

Section: Discussionsupporting

confidence: 88%

Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis)

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 88%

Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis)

et al. 2019

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“…This may be relevant since some studies show that the release of high NO levels may be toxic to the cells themselves. 34 The in vitro experiments clearly revealed that Canova medication can modulate macrophage infection by Leishmania. For this reason, we performed experiments to examine whether the medication might affect infection by L. (L.) amazonensis in vivo.…”

Section: Discussionmentioning

confidence: 98%

Immunomodulatory effect of Canova medication on experimental infection

Pereira

Lonardoni

Grespan

et al. 2005

Journal of Infection

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“…Six HAV genotypes are recognized with genotypes IeIII containing primarily human isolates and genotypes IVeVI containing simian isolates. A variety of nonhuman primates may be infected experimentally with human HAV isolates (Pinto et al, 2000;Amado et al, 2010). A great wealth of information exists on the experimental infection of tamarins.…”

Section: Etiologymentioning

confidence: 99%