An essential role of PI3K in the control of West Nile virus infection

Abstract The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flavivira...

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Autores principales:	Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f12efa4358a34f168c265e104bd89c2a
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spelling	oai:doaj.org-article:f12efa4358a34f168c265e104bd89c2a2021-12-02T11:40:50ZAn essential role of PI3K in the control of West Nile virus infection10.1038/s41598-017-03912-52045-2322https://doaj.org/article/f12efa4358a34f168c265e104bd89c2a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03912-5https://doaj.org/toc/2045-2322Abstract The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3–16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines. Both 3-MA and LY repressed IFN-I mRNA and protein expression significantly. Surprisingly, WM enhanced the mRNA expression of IFN-I and TNF-α, and TNF-α protein production modestly, while dramatically decreased the secreted IFN-I. Further studies showed that the catalytic subunit p110δ of class I PI3K played a role in induction of antiviral immune responses. Lastly translocation of interferon regulatory factor 7(IRF7) from the cytosol to the nuclei was effectively blocked in the presence of PI3K inhibitors. Our results clearly define an antiviral role of PI3K by modulating immune responses and demonstrate differential mode of action of three PI3K inhibitors on IFN-I.Leilei WangLong YangErol FikrigPenghua WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leilei Wang Long Yang Erol Fikrig Penghua Wang An essential role of PI3K in the control of West Nile virus infection
description	Abstract The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3–16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines. Both 3-MA and LY repressed IFN-I mRNA and protein expression significantly. Surprisingly, WM enhanced the mRNA expression of IFN-I and TNF-α, and TNF-α protein production modestly, while dramatically decreased the secreted IFN-I. Further studies showed that the catalytic subunit p110δ of class I PI3K played a role in induction of antiviral immune responses. Lastly translocation of interferon regulatory factor 7(IRF7) from the cytosol to the nuclei was effectively blocked in the presence of PI3K inhibitors. Our results clearly define an antiviral role of PI3K by modulating immune responses and demonstrate differential mode of action of three PI3K inhibitors on IFN-I.
format	article
author	Leilei Wang Long Yang Erol Fikrig Penghua Wang
author_facet	Leilei Wang Long Yang Erol Fikrig Penghua Wang
author_sort	Leilei Wang
title	An essential role of PI3K in the control of West Nile virus infection
title_short	An essential role of PI3K in the control of West Nile virus infection
title_full	An essential role of PI3K in the control of West Nile virus infection
title_fullStr	An essential role of PI3K in the control of West Nile virus infection
title_full_unstemmed	An essential role of PI3K in the control of West Nile virus infection
title_sort	essential role of pi3k in the control of west nile virus infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f12efa4358a34f168c265e104bd89c2a
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An essential role of PI3K in the control of West Nile virus infection

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