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Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells
Neonatal microcephaly and adult Guillain–Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility gr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776752/ https://www.ncbi.nlm.nih.gov/pubmed/35058496 http://dx.doi.org/10.1038/s41598-022-04955-z |
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author | Chin, Kim-Ling Zainal, Nurhafiza Sam, Sing-Sin Hassandarvish, Pouya Lani, Rafidah AbuBakar, Sazaly |
author_facet | Chin, Kim-Ling Zainal, Nurhafiza Sam, Sing-Sin Hassandarvish, Pouya Lani, Rafidah AbuBakar, Sazaly |
author_sort | Chin, Kim-Ling |
collection | PubMed |
description | Neonatal microcephaly and adult Guillain–Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1’s role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug, and HMGB1-knockdown (shHMGB1) Huh7 cells. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a > 99% increase in the cytosolic HMGB1 expression at 72-h post-infection (h.p.i). The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)-dependent manner. Treatment of the ZIKV-infected cells with dexamethasone (150 µM) reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (P < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (P < 0.01). The antiviral effects, however, were not observed in the dexamethasone-treated shHMGB1 cells. These results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation by dexamethasone coincided with a reduction in ZIKV replication. These findings highlight the potential of targeting the localization of HMGB1 in affecting ZIKV infection. |
format | Online Article Text |
id | pubmed-8776752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87767522022-01-24 Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells Chin, Kim-Ling Zainal, Nurhafiza Sam, Sing-Sin Hassandarvish, Pouya Lani, Rafidah AbuBakar, Sazaly Sci Rep Article Neonatal microcephaly and adult Guillain–Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1’s role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug, and HMGB1-knockdown (shHMGB1) Huh7 cells. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a > 99% increase in the cytosolic HMGB1 expression at 72-h post-infection (h.p.i). The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)-dependent manner. Treatment of the ZIKV-infected cells with dexamethasone (150 µM) reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (P < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (P < 0.01). The antiviral effects, however, were not observed in the dexamethasone-treated shHMGB1 cells. These results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation by dexamethasone coincided with a reduction in ZIKV replication. These findings highlight the potential of targeting the localization of HMGB1 in affecting ZIKV infection. Nature Publishing Group UK 2022-01-20 /pmc/articles/PMC8776752/ /pubmed/35058496 http://dx.doi.org/10.1038/s41598-022-04955-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chin, Kim-Ling Zainal, Nurhafiza Sam, Sing-Sin Hassandarvish, Pouya Lani, Rafidah AbuBakar, Sazaly Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title | Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title_full | Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title_fullStr | Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title_full_unstemmed | Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title_short | Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells |
title_sort | intracellular translocation of hmgb1 is important for zika virus replication in huh7 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776752/ https://www.ncbi.nlm.nih.gov/pubmed/35058496 http://dx.doi.org/10.1038/s41598-022-04955-z |
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