The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the most severe forms of dengue virus infection with hemorrhage and plasma leakage. However, pathogenic mechanisms of DHF and DSS remain poorly understood. We therefore investigated host responses as determined by changes in the cell...
Saved in:
Main Authors: | , , , , |
---|---|
Other Authors: | |
Format: | Article |
Published: |
2018
|
Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/28634 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Mahidol University |
id |
th-mahidol.28634 |
---|---|
record_format |
dspace |
spelling |
th-mahidol.286342018-09-24T15:53:08Z The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells Rattiyaporn Kanlaya Sa Nga Pattanakitsakul Supachok Sinchaikul Shui Tein Chen Visith Thongboonkerd Mahidol University Genomics Research Center, Academia Sinica National Taiwan University Biochemistry, Genetics and Molecular Biology Chemistry Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the most severe forms of dengue virus infection with hemorrhage and plasma leakage. However, pathogenic mechanisms of DHF and DSS remain poorly understood. We therefore investigated host responses as determined by changes in the cellular proteome of primary human endothelial cells upon infection with dengue virus serotype 2 (DEN-2) at a multiplicity of infection (MOI) of 10 for 24 h. Two-dimensional PAGE and quantitative intensity analysis revealed 38 significantly altered protein spots (16 upregulated and 22 downregulated) in DEN-2-infected cells compared to mock controls. These altered proteins were successfully identified by mass spectrometry, including those involved in oxidative stress response, transcription and translation, cytoskeleton assembly, protein degradation, cell growth regulation, apoptosis, cellular metabolism, and antiviral response. The proteomic data were validated by Western blot analyses [upregulated ubiquitin-activating enzyme E1 (UBE1) and downregulated annexin A2] and an immunofluorescence study (upregulated MxA). Interestingly, we found that MxA was colocalized with DEN-2 viral capsid protein, strengthening its role as an antiviral protein. Moreover, we also identified upregulation of a proteasome subunit. Our functional study revealed the significant role of ubiquitination in dengue infection and UBE1 inhibition by its specific inhibitor (UBEI-41) caused a significant reduction in the level of viral protein synthesis and its infectivity. Our findings suggest that various biological processes were triggered in response to dengue infection, particularly antiviral IFN and ubiquitin-proteasome pathways. © 2010 American Chemical Society. 2018-09-24T08:42:43Z 2018-09-24T08:42:43Z 2010-10-01 Article Journal of Proteome Research. Vol.9, No.10 (2010), 4960-4971 10.1021/pr100219y 15353907 15353893 2-s2.0-77957366917 https://repository.li.mahidol.ac.th/handle/123456789/28634 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77957366917&origin=inward |
institution |
Mahidol University |
building |
Mahidol University Library |
continent |
Asia |
country |
Thailand Thailand |
content_provider |
Mahidol University Library |
collection |
Mahidol University Institutional Repository |
topic |
Biochemistry, Genetics and Molecular Biology Chemistry |
spellingShingle |
Biochemistry, Genetics and Molecular Biology Chemistry Rattiyaporn Kanlaya Sa Nga Pattanakitsakul Supachok Sinchaikul Shui Tein Chen Visith Thongboonkerd The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
description |
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the most severe forms of dengue virus infection with hemorrhage and plasma leakage. However, pathogenic mechanisms of DHF and DSS remain poorly understood. We therefore investigated host responses as determined by changes in the cellular proteome of primary human endothelial cells upon infection with dengue virus serotype 2 (DEN-2) at a multiplicity of infection (MOI) of 10 for 24 h. Two-dimensional PAGE and quantitative intensity analysis revealed 38 significantly altered protein spots (16 upregulated and 22 downregulated) in DEN-2-infected cells compared to mock controls. These altered proteins were successfully identified by mass spectrometry, including those involved in oxidative stress response, transcription and translation, cytoskeleton assembly, protein degradation, cell growth regulation, apoptosis, cellular metabolism, and antiviral response. The proteomic data were validated by Western blot analyses [upregulated ubiquitin-activating enzyme E1 (UBE1) and downregulated annexin A2] and an immunofluorescence study (upregulated MxA). Interestingly, we found that MxA was colocalized with DEN-2 viral capsid protein, strengthening its role as an antiviral protein. Moreover, we also identified upregulation of a proteasome subunit. Our functional study revealed the significant role of ubiquitination in dengue infection and UBE1 inhibition by its specific inhibitor (UBEI-41) caused a significant reduction in the level of viral protein synthesis and its infectivity. Our findings suggest that various biological processes were triggered in response to dengue infection, particularly antiviral IFN and ubiquitin-proteasome pathways. © 2010 American Chemical Society. |
author2 |
Mahidol University |
author_facet |
Mahidol University Rattiyaporn Kanlaya Sa Nga Pattanakitsakul Supachok Sinchaikul Shui Tein Chen Visith Thongboonkerd |
format |
Article |
author |
Rattiyaporn Kanlaya Sa Nga Pattanakitsakul Supachok Sinchaikul Shui Tein Chen Visith Thongboonkerd |
author_sort |
Rattiyaporn Kanlaya |
title |
The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
title_short |
The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
title_full |
The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
title_fullStr |
The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
title_full_unstemmed |
The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
title_sort |
ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/28634 |
_version_ |
1763492899039739904 |