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...

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Autores principales: Panwar, Aleksha, Wangchuk, Jigme, Kar, Meenakshi, Lodha, Rakesh, Medigeshi, Guruprasad R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
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.
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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
title_full Dengue virus replication enhances labile zinc pools by modulation of ZIP8
title_fullStr Dengue virus replication enhances labile zinc pools by modulation of ZIP8
title_full_unstemmed Dengue virus replication enhances labile zinc pools by modulation of ZIP8
title_short Dengue virus replication enhances labile zinc pools by modulation of ZIP8
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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