Macropinocytosis dependent entry of Chikungunya virus into human muscle cells

Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection w...

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Autores principales: Lee, Ching Hua, Regina, Mohamed Hussain, Khairunnisa, Chu, Justin Jang Hann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730948/
https://www.ncbi.nlm.nih.gov/pubmed/31449523
http://dx.doi.org/10.1371/journal.pntd.0007610
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author Lee, Ching Hua, Regina
Mohamed Hussain, Khairunnisa
Chu, Justin Jang Hann
author_facet Lee, Ching Hua, Regina
Mohamed Hussain, Khairunnisa
Chu, Justin Jang Hann
author_sort Lee, Ching Hua, Regina
collection PubMed
description Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection was evaluated. CHIKV infection was found to be cell-type dependent and virus strain-specific. Furthermore, SJCRH30 (human rhabdomyosarcoma cell line) was showed to be highly permissive to CHIKV infection, with maximum production of infectious virions observed at 12 h.p.i. Pre-infection treatment of SJCRH30 with various inhibitors of endocytosis, including monodansylcadaverine (receptor-mediated endocytic inhibitor), dynasore (clathrin-mediated endocytic inhibitor), as well as filipin (caveolin-mediated endocytosis inhibitor), resulted in minimal inhibition of CHIKV infection. In contrast, dose-dependent inhibition of CHIKV infection was observed with the treatment of macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Furthermore, siRNA-mediated knockdown of sortin nexin 9 (SNX9) a protein involved in macropinosome formation, also resulted in a significant dose-dependent reduction in viral titre. By performing a virus entry assay, CHIKV particles were also observed to colocalize with FITC-dextran, a macropinosome marker. This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the data from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells.
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spelling pubmed-67309482019-09-16 Macropinocytosis dependent entry of Chikungunya virus into human muscle cells Lee, Ching Hua, Regina Mohamed Hussain, Khairunnisa Chu, Justin Jang Hann PLoS Negl Trop Dis Research Article Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection was evaluated. CHIKV infection was found to be cell-type dependent and virus strain-specific. Furthermore, SJCRH30 (human rhabdomyosarcoma cell line) was showed to be highly permissive to CHIKV infection, with maximum production of infectious virions observed at 12 h.p.i. Pre-infection treatment of SJCRH30 with various inhibitors of endocytosis, including monodansylcadaverine (receptor-mediated endocytic inhibitor), dynasore (clathrin-mediated endocytic inhibitor), as well as filipin (caveolin-mediated endocytosis inhibitor), resulted in minimal inhibition of CHIKV infection. In contrast, dose-dependent inhibition of CHIKV infection was observed with the treatment of macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Furthermore, siRNA-mediated knockdown of sortin nexin 9 (SNX9) a protein involved in macropinosome formation, also resulted in a significant dose-dependent reduction in viral titre. By performing a virus entry assay, CHIKV particles were also observed to colocalize with FITC-dextran, a macropinosome marker. This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the data from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells. Public Library of Science 2019-08-26 /pmc/articles/PMC6730948/ /pubmed/31449523 http://dx.doi.org/10.1371/journal.pntd.0007610 Text en © 2019 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Ching Hua, Regina
Mohamed Hussain, Khairunnisa
Chu, Justin Jang Hann
Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title_full Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title_fullStr Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title_full_unstemmed Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title_short Macropinocytosis dependent entry of Chikungunya virus into human muscle cells
title_sort macropinocytosis dependent entry of chikungunya virus into human muscle cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730948/
https://www.ncbi.nlm.nih.gov/pubmed/31449523
http://dx.doi.org/10.1371/journal.pntd.0007610
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