PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes

Astrocytes are a main target of JC polyomavirus (JCPyV) in the central nervous system (CNS), where the destruction of these cells, along with oligodendrocytes, leads to the fatal disease progressive multifocal leukoencephalopathy (PML). There is no cure currently available for PML, so it is essentia...

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Main Authors:	Michael P. Wilczek, Francesca J. Armstrong, Colleen L. Mayberry, Benjamin L. King, Melissa S. Maginnis
Format:	article
Language:	EN
Published:	MDPI AG 2021
Subjects:	JC polyomavirus PML astrocytes SVGA cells primary cells PI3K Biology (General) QH301-705.5
Online Access:	https://doaj.org/article/6870eeaa06274f46a914f777622eabd3
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spelling	oai:doaj.org-article:6870eeaa06274f46a914f777622eabd32021-11-25T17:13:00ZPI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes10.3390/cells101132182073-4409https://doaj.org/article/6870eeaa06274f46a914f777622eabd32021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3218https://doaj.org/toc/2073-4409Astrocytes are a main target of JC polyomavirus (JCPyV) in the central nervous system (CNS), where the destruction of these cells, along with oligodendrocytes, leads to the fatal disease progressive multifocal leukoencephalopathy (PML). There is no cure currently available for PML, so it is essential to discover antivirals for this aggressive disease. Additionally, the lack of a tractable in vivo models for studying JCPyV infection makes primary cells an accurate alternative for elucidating mechanisms of viral infection in the CNS. This research to better understand the signaling pathways activated in response to JCPyV infection reveals and establishes the importance of the PI3K/AKT/mTOR signaling pathway in JCPyV infection in primary human astrocytes compared to transformed cell lines. Using RNA sequencing and chemical inhibitors to target PI3K, AKT, and mTOR, we have demonstrated the importance of this signaling pathway in JCPyV infection of primary astrocytes not observed in transformed cells. Collectively, these findings illuminate the potential for repurposing drugs that are involved with inhibition of the PI3K/AKT/mTOR signaling pathway and cancer treatment as potential therapeutics for PML, caused by this neuroinvasive virus.Michael P. WilczekFrancesca J. ArmstrongColleen L. MayberryBenjamin L. KingMelissa S. MaginnisMDPI AGarticleJC polyomavirusPMLastrocytesSVGA cellsprimary cellsPI3KBiology (General)QH301-705.5ENCells, Vol 10, Iss 3218, p 3218 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	JC polyomavirus PML astrocytes SVGA cells primary cells PI3K Biology (General) QH301-705.5
spellingShingle	JC polyomavirus PML astrocytes SVGA cells primary cells PI3K Biology (General) QH301-705.5 Michael P. Wilczek Francesca J. Armstrong Colleen L. Mayberry Benjamin L. King Melissa S. Maginnis PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
description	Astrocytes are a main target of JC polyomavirus (JCPyV) in the central nervous system (CNS), where the destruction of these cells, along with oligodendrocytes, leads to the fatal disease progressive multifocal leukoencephalopathy (PML). There is no cure currently available for PML, so it is essential to discover antivirals for this aggressive disease. Additionally, the lack of a tractable in vivo models for studying JCPyV infection makes primary cells an accurate alternative for elucidating mechanisms of viral infection in the CNS. This research to better understand the signaling pathways activated in response to JCPyV infection reveals and establishes the importance of the PI3K/AKT/mTOR signaling pathway in JCPyV infection in primary human astrocytes compared to transformed cell lines. Using RNA sequencing and chemical inhibitors to target PI3K, AKT, and mTOR, we have demonstrated the importance of this signaling pathway in JCPyV infection of primary astrocytes not observed in transformed cells. Collectively, these findings illuminate the potential for repurposing drugs that are involved with inhibition of the PI3K/AKT/mTOR signaling pathway and cancer treatment as potential therapeutics for PML, caused by this neuroinvasive virus.
format	article
author	Michael P. Wilczek Francesca J. Armstrong Colleen L. Mayberry Benjamin L. King Melissa S. Maginnis
author_facet	Michael P. Wilczek Francesca J. Armstrong Colleen L. Mayberry Benjamin L. King Melissa S. Maginnis
author_sort	Michael P. Wilczek
title	PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
title_short	PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
title_full	PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
title_fullStr	PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
title_full_unstemmed	PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes
title_sort	pi3k/akt/mtor signaling pathway is required for jcpyv infection in primary astrocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6870eeaa06274f46a914f777622eabd3
work_keys_str_mv	AT michaelpwilczek pi3kaktmtorsignalingpathwayisrequiredforjcpyvinfectioninprimaryastrocytes AT francescajarmstrong pi3kaktmtorsignalingpathwayisrequiredforjcpyvinfectioninprimaryastrocytes AT colleenlmayberry pi3kaktmtorsignalingpathwayisrequiredforjcpyvinfectioninprimaryastrocytes AT benjaminlking pi3kaktmtorsignalingpathwayisrequiredforjcpyvinfectioninprimaryastrocytes AT melissasmaginnis pi3kaktmtorsignalingpathwayisrequiredforjcpyvinfectioninprimaryastrocytes
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PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes

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