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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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Autores principales: Wodrich, Harald, Henaff, Daniel, Jammart, Baptist, Segura-Morales, Carolina, Seelmeir, Sigrid, Coux, Olivier, Ruzsics, Zsolt, Wiethoff, Christopher M., Kremer, Eric J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841620/
https://www.ncbi.nlm.nih.gov/pubmed/20333243
http://dx.doi.org/10.1371/journal.ppat.1000808
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author Wodrich, Harald
Henaff, Daniel
Jammart, Baptist
Segura-Morales, Carolina
Seelmeir, Sigrid
Coux, Olivier
Ruzsics, Zsolt
Wiethoff, Christopher M.
Kremer, Eric J.
author_facet Wodrich, Harald
Henaff, Daniel
Jammart, Baptist
Segura-Morales, Carolina
Seelmeir, Sigrid
Coux, Olivier
Ruzsics, Zsolt
Wiethoff, Christopher M.
Kremer, Eric J.
author_sort Wodrich, Harald
collection PubMed
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 pubmed-28416202010-03-24 A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry Wodrich, Harald Henaff, Daniel Jammart, Baptist Segura-Morales, Carolina Seelmeir, Sigrid Coux, Olivier Ruzsics, Zsolt Wiethoff, Christopher M. Kremer, Eric J. PLoS Pathog Research Article 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. Public Library of Science 2010-03-19 /pmc/articles/PMC2841620/ /pubmed/20333243 http://dx.doi.org/10.1371/journal.ppat.1000808 Text en Wodrich 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wodrich, Harald
Henaff, Daniel
Jammart, Baptist
Segura-Morales, Carolina
Seelmeir, Sigrid
Coux, Olivier
Ruzsics, Zsolt
Wiethoff, Christopher M.
Kremer, Eric J.
A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841620/
https://www.ncbi.nlm.nih.gov/pubmed/20333243
http://dx.doi.org/10.1371/journal.ppat.1000808
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