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Open AccessArticle

Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever

1
Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
2
Department of Medical Research, Ministry of Health and Sports, Yangon 11191, Myanmar
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Department of Pathology, Pathology Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
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Division of Dengue Hemorrhagic Fever Research, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
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National Health Laboratory, Yangon 11181, Myanmar
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Center for Vaccine Development, Mahidol University, Nakhon Pathom 73170, Thailand
7
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
Trop. Med. Infect. Dis. 2019, 4(2), 63; https://doi.org/10.3390/tropicalmed4020063
Received: 22 February 2019 / Revised: 28 March 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
(This article belongs to the Special Issue Epidemiology of Dengue: Past, Present and Future)
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. View Full-Text
Keywords: dengue virus; dengue hemorrhagic fever; ultrastructure; electron microscope; suckling mouse brain; liver; autopsy dengue virus; dengue hemorrhagic fever; ultrastructure; electron microscope; suckling mouse brain; liver; autopsy
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Win, M.M.; Charngkaew, K.; Punyadee, N.; Aye, K.S.; Win, N.; Chaisri, U.; Chomanee, N.; Avirutnan, P.; Yoksan, S.; Malasit, P. Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever. Trop. Med. Infect. Dis. 2019, 4, 63.

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