Dengue virus replication enhances labile zinc pools by modulation of ZIP8
Zinc‐dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life‐cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolis...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612096/ https://www.ncbi.nlm.nih.gov/pubmed/34619004 http://dx.doi.org/10.1111/cmi.13395 |
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author | Panwar, Aleksha Wangchuk, Jigme Kar, Meenakshi Lodha, Rakesh Medigeshi, Guruprasad R. |
author_facet | Panwar, Aleksha Wangchuk, Jigme Kar, Meenakshi Lodha, Rakesh Medigeshi, Guruprasad R. |
author_sort | Panwar, Aleksha |
collection | PubMed |
description | Zinc‐dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life‐cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV‐inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA‐mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection. TAKE AWAYS: Dengue virus utilises cellular zinc homeostasis during replication of its RNA. ZIP8 upregulates free zinc levels during dengue virus replication. Enhanced viremia associates with elevated intracellular free zinc in dengue. |
format | Online Article Text |
id | pubmed-7612096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76120962021-12-10 Dengue virus replication enhances labile zinc pools by modulation of ZIP8 Panwar, Aleksha Wangchuk, Jigme Kar, Meenakshi Lodha, Rakesh Medigeshi, Guruprasad R. Cell Microbiol Breaking Report Zinc‐dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life‐cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV‐inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA‐mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection. TAKE AWAYS: Dengue virus utilises cellular zinc homeostasis during replication of its RNA. ZIP8 upregulates free zinc levels during dengue virus replication. Enhanced viremia associates with elevated intracellular free zinc in dengue. John Wiley & Sons, Inc. 2021-10-15 2021-12 /pmc/articles/PMC7612096/ /pubmed/34619004 http://dx.doi.org/10.1111/cmi.13395 Text en © 2021 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Breaking Report Panwar, Aleksha Wangchuk, Jigme Kar, Meenakshi Lodha, Rakesh Medigeshi, Guruprasad R. Dengue virus replication enhances labile zinc pools by modulation of ZIP8 |
title | Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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title_full | Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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title_fullStr | Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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title_full_unstemmed | Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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title_short | Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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title_sort | dengue virus replication enhances labile zinc pools by modulation of zip8 |
topic | Breaking Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612096/ https://www.ncbi.nlm.nih.gov/pubmed/34619004 http://dx.doi.org/10.1111/cmi.13395 |
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