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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...

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Autores principales: Win, Min Min, Charngkaew, Komgrid, Punyadee, Nuntaya, Aye, Khin Saw, Win, Ne, Chaisri, Urai, Chomanee, Nusara, Avirutnan, Panisadee, Yoksan, Sutee, Malasit, Prida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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