Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses

ABSTRACT Receptor-mediated endocytosis is a cellular process commonly hijacked by viruses to enter cells. The stages of entry are well described for certain viruses, but the host factors that mediate each step are less well characterized. We previously identified endosomal cation channel mucolipin-2...

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Autores principales:	Nicholas Rinkenberger, John W. Schoggins
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	endocytosis flavivirus influenza ion channels vesicular trafficking virus entry Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0372d3e358da4ac39b27f1c4b2cf0d44
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spelling	oai:doaj.org-article:0372d3e358da4ac39b27f1c4b2cf0d442021-11-15T15:53:26ZMucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses10.1128/mBio.02314-172150-7511https://doaj.org/article/0372d3e358da4ac39b27f1c4b2cf0d442018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02314-17https://doaj.org/toc/2150-7511ABSTRACT Receptor-mediated endocytosis is a cellular process commonly hijacked by viruses to enter cells. The stages of entry are well described for certain viruses, but the host factors that mediate each step are less well characterized. We previously identified endosomal cation channel mucolipin-2 (MCOLN2) as a host factor that promotes viral infection. Here, we assign a role for MCOLN2 in modulating viral entry. We show that MCOLN2 specifically promotes viral vesicular trafficking and subsequent escape from endosomal compartments. This mechanism requires channel activity, occurs independently of antiviral signaling, and broadly applies to enveloped RNA viruses that require transport to late endosomes for infection, including influenza A virus, yellow fever virus, and Zika virus. We further identify a rare allelic variant of human MCOLN2 that has a loss-of-function phenotype with respect to viral enhancement. These findings establish a mechanistic link between an endosomal cation channel and late stages of viral entry. IMPORTANCE Viruses must co-opt cellular processes to complete their life cycle. To enter cells, viruses frequently take advantage of cellular receptor-mediated endocytosis pathways. A growing number of host proteins are implicated in these viral uptake pathways. Here, we describe a new role for the gated cation channel MCOLN2 in viral entry. This endosomal protein modulates viral entry by enhancing the efficiency of viral trafficking through the endosomal system. Thus, MCOLN2-mediated enhancement of infection may represent a key vulnerability in the viral life cycle that could be targeted for therapeutic intervention.Nicholas RinkenbergerJohn W. SchogginsAmerican Society for Microbiologyarticleendocytosisflavivirusinfluenzaion channelsvesicular traffickingvirus entryMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	endocytosis flavivirus influenza ion channels vesicular trafficking virus entry Microbiology QR1-502
spellingShingle	endocytosis flavivirus influenza ion channels vesicular trafficking virus entry Microbiology QR1-502 Nicholas Rinkenberger John W. Schoggins Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
description	ABSTRACT Receptor-mediated endocytosis is a cellular process commonly hijacked by viruses to enter cells. The stages of entry are well described for certain viruses, but the host factors that mediate each step are less well characterized. We previously identified endosomal cation channel mucolipin-2 (MCOLN2) as a host factor that promotes viral infection. Here, we assign a role for MCOLN2 in modulating viral entry. We show that MCOLN2 specifically promotes viral vesicular trafficking and subsequent escape from endosomal compartments. This mechanism requires channel activity, occurs independently of antiviral signaling, and broadly applies to enveloped RNA viruses that require transport to late endosomes for infection, including influenza A virus, yellow fever virus, and Zika virus. We further identify a rare allelic variant of human MCOLN2 that has a loss-of-function phenotype with respect to viral enhancement. These findings establish a mechanistic link between an endosomal cation channel and late stages of viral entry. IMPORTANCE Viruses must co-opt cellular processes to complete their life cycle. To enter cells, viruses frequently take advantage of cellular receptor-mediated endocytosis pathways. A growing number of host proteins are implicated in these viral uptake pathways. Here, we describe a new role for the gated cation channel MCOLN2 in viral entry. This endosomal protein modulates viral entry by enhancing the efficiency of viral trafficking through the endosomal system. Thus, MCOLN2-mediated enhancement of infection may represent a key vulnerability in the viral life cycle that could be targeted for therapeutic intervention.
format	article
author	Nicholas Rinkenberger John W. Schoggins
author_facet	Nicholas Rinkenberger John W. Schoggins
author_sort	Nicholas Rinkenberger
title	Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
title_short	Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
title_full	Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
title_fullStr	Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
title_full_unstemmed	Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses
title_sort	mucolipin-2 cation channel increases trafficking efficiency of endocytosed viruses
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/0372d3e358da4ac39b27f1c4b2cf0d44
work_keys_str_mv	AT nicholasrinkenberger mucolipin2cationchannelincreasestraffickingefficiencyofendocytosedviruses AT johnwschoggins mucolipin2cationchannelincreasestraffickingefficiencyofendocytosedviruses
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Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses

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