Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target.
Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monk...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6168161?pdf=render |
| _version_ | 1818926345506258944 |
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| author | Fernanda de Oliveira Bottino Noemi Rovaris Gardinali Sarah Beatriz Salamene Salvador Andreza Soriano Figueiredo Lynn Barwick Cysne Juliane Siqueira Francisco Jaqueline Mendes de Oliveira Marcelo Pelajo Machado Marcelo Alves Pinto |
| author_facet | Fernanda de Oliveira Bottino Noemi Rovaris Gardinali Sarah Beatriz Salamene Salvador Andreza Soriano Figueiredo Lynn Barwick Cysne Juliane Siqueira Francisco Jaqueline Mendes de Oliveira Marcelo Pelajo Machado Marcelo Alves Pinto |
| author_sort | Fernanda de Oliveira Bottino |
| collection | DOAJ |
| description | Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation. |
| first_indexed | 2024-12-20T02:55:39Z |
| format | Article |
| id | doaj.art-56cbba4288654470b5ae3af2311c83e6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:55:39Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-56cbba4288654470b5ae3af2311c83e62022-12-21T19:55:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020503910.1371/journal.pone.0205039Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target.Fernanda de Oliveira BottinoNoemi Rovaris GardinaliSarah Beatriz Salamene SalvadorAndreza Soriano FigueiredoLynn Barwick CysneJuliane Siqueira FranciscoJaqueline Mendes de OliveiraMarcelo Pelajo MachadoMarcelo Alves PintoHepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation.http://europepmc.org/articles/PMC6168161?pdf=render |
| spellingShingle | Fernanda de Oliveira Bottino Noemi Rovaris Gardinali Sarah Beatriz Salamene Salvador Andreza Soriano Figueiredo Lynn Barwick Cysne Juliane Siqueira Francisco Jaqueline Mendes de Oliveira Marcelo Pelajo Machado Marcelo Alves Pinto Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. PLoS ONE |
| title | Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. |
| title_full | Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. |
| title_fullStr | Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. |
| title_full_unstemmed | Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. |
| title_short | Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target. |
| title_sort | cynomolgus monkeys macaca fascicularis experimentally and naturally infected with hepatitis e virus the bone marrow as a possible new viral target |
| url | http://europepmc.org/articles/PMC6168161?pdf=render |
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