A capsid-encoded PPxY-motif facilitates adenovirus entry.

Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated...

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Main Authors: Harald Wodrich, Daniel Henaff, Baptist Jammart, Carolina Segura-Morales, Sigrid Seelmeir, Olivier Coux, Zsolt Ruzsics, Christopher M Wiethoff, Eric J Kremer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-03-01
Series:PLoS Pathogens
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333243/pdf/?tool=EBI
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author Harald Wodrich
Daniel Henaff
Baptist Jammart
Carolina Segura-Morales
Sigrid Seelmeir
Olivier Coux
Zsolt Ruzsics
Christopher M Wiethoff
Eric J Kremer
author_facet Harald Wodrich
Daniel Henaff
Baptist Jammart
Carolina Segura-Morales
Sigrid Seelmeir
Olivier Coux
Zsolt Ruzsics
Christopher M Wiethoff
Eric J Kremer
author_sort Harald Wodrich
collection DOAJ
description Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens.
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spelling doaj.art-ca71ac1e8ace4d4aa1b5123ec554c75a2022-12-21T20:36:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-03-0163e100080810.1371/journal.ppat.1000808A capsid-encoded PPxY-motif facilitates adenovirus entry.Harald WodrichDaniel HenaffBaptist JammartCarolina Segura-MoralesSigrid SeelmeirOlivier CouxZsolt RuzsicsChristopher M WiethoffEric J KremerViruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333243/pdf/?tool=EBI
spellingShingle Harald Wodrich
Daniel Henaff
Baptist Jammart
Carolina Segura-Morales
Sigrid Seelmeir
Olivier Coux
Zsolt Ruzsics
Christopher M Wiethoff
Eric J Kremer
A capsid-encoded PPxY-motif facilitates adenovirus entry.
PLoS Pathogens
title A capsid-encoded PPxY-motif facilitates adenovirus entry.
title_full A capsid-encoded PPxY-motif facilitates adenovirus entry.
title_fullStr A capsid-encoded PPxY-motif facilitates adenovirus entry.
title_full_unstemmed A capsid-encoded PPxY-motif facilitates adenovirus entry.
title_short A capsid-encoded PPxY-motif facilitates adenovirus entry.
title_sort capsid encoded ppxy motif facilitates adenovirus entry
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333243/pdf/?tool=EBI
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