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Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever
Recent advances in electron microscopy and tomography have revealed distinct virus-induced endoplasmic reticulum (ER) structures unique for dengue virus (DV) and other flaviviruses in cell culture models, including hepatocytes. These altered ultrastructures serve as sites for viral replication. In t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631216/ https://www.ncbi.nlm.nih.gov/pubmed/31013708 http://dx.doi.org/10.3390/tropicalmed4020063 |
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author | Win, Min Min Charngkaew, Komgrid Punyadee, Nuntaya Aye, Khin Saw Win, Ne Chaisri, Urai Chomanee, Nusara Avirutnan, Panisadee Yoksan, Sutee Malasit, Prida |
author_facet | Win, Min Min Charngkaew, Komgrid Punyadee, Nuntaya Aye, Khin Saw Win, Ne Chaisri, Urai Chomanee, Nusara Avirutnan, Panisadee Yoksan, Sutee Malasit, Prida |
author_sort | Win, Min Min |
collection | PubMed |
description | Recent advances in electron microscopy and tomography have revealed distinct virus-induced endoplasmic reticulum (ER) structures unique for dengue virus (DV) and other flaviviruses in cell culture models, including hepatocytes. These altered ultrastructures serve as sites for viral replication. In this study, we used transmission electron microscopy to investigate whether such structures were present in the liver of fatal dengue hemorrhagic fever (DHF) autopsy cases. In parallel, electron microscopic examination of suckling mouse brains experimentally infected with DV was performed as an in vivo model of acute DV infection. Typical features of ER changes containing abundance of replicative virions were observed in neurons and microglia of DV-infected suckling mouse brains (SMB). This indicated that the in vivo DV infection could induce similar viral replication structures as previously described in the in vitro DV-infected cell model. Nevertheless, liver tissues from autopsy of patients who died of DHF showed scant changes of ER membrane structures and rare particles of virions in hepatocytes, despite overwhelming evidence for the presence of viral antigens and RNA–indicating active virus replication. Instead hepatocytes contained an abundance of steatotic vesicles and structural damages. This lack of structural changes indicative of virus replication in human hepatocytes is discussed. |
format | Online Article Text |
id | pubmed-6631216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66312162019-08-19 Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever Win, Min Min Charngkaew, Komgrid Punyadee, Nuntaya Aye, Khin Saw Win, Ne Chaisri, Urai Chomanee, Nusara Avirutnan, Panisadee Yoksan, Sutee Malasit, Prida Trop Med Infect Dis Article Recent advances in electron microscopy and tomography have revealed distinct virus-induced endoplasmic reticulum (ER) structures unique for dengue virus (DV) and other flaviviruses in cell culture models, including hepatocytes. These altered ultrastructures serve as sites for viral replication. In this study, we used transmission electron microscopy to investigate whether such structures were present in the liver of fatal dengue hemorrhagic fever (DHF) autopsy cases. In parallel, electron microscopic examination of suckling mouse brains experimentally infected with DV was performed as an in vivo model of acute DV infection. Typical features of ER changes containing abundance of replicative virions were observed in neurons and microglia of DV-infected suckling mouse brains (SMB). This indicated that the in vivo DV infection could induce similar viral replication structures as previously described in the in vitro DV-infected cell model. Nevertheless, liver tissues from autopsy of patients who died of DHF showed scant changes of ER membrane structures and rare particles of virions in hepatocytes, despite overwhelming evidence for the presence of viral antigens and RNA–indicating active virus replication. Instead hepatocytes contained an abundance of steatotic vesicles and structural damages. This lack of structural changes indicative of virus replication in human hepatocytes is discussed. MDPI 2019-04-12 /pmc/articles/PMC6631216/ /pubmed/31013708 http://dx.doi.org/10.3390/tropicalmed4020063 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Win, Min Min Charngkaew, Komgrid Punyadee, Nuntaya Aye, Khin Saw Win, Ne Chaisri, Urai Chomanee, Nusara Avirutnan, Panisadee Yoksan, Sutee Malasit, Prida Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title | Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title_full | Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title_fullStr | Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title_full_unstemmed | Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title_short | Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever |
title_sort | ultrastructural features of human liver specimens from patients who died of dengue hemorrhagic fever |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631216/ https://www.ncbi.nlm.nih.gov/pubmed/31013708 http://dx.doi.org/10.3390/tropicalmed4020063 |
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