HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells

HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells

Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified...

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Main Authors: Stanton, Richard J., Prod’homme, Virginie, Purbhoo, Marco A., Moore, Melanie, Aicheler, Rebecca J., Heinzmann, Marcus, Bailer, Susanne M., Haas, Jürgen, Antrobus, Robin, Weekes, Michael P., Lehner, Paul J., Vojtesek, Borivoj, Miners, Kelly L., Man, Stephen, Wilkie, Gavin S., Davison, Andrew J., Wang, Eddie C.Y., Tomasec, Peter, Wilkinson, Gavin W.G.
Format: Online
Language:English
Published: Cell Press 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150922/
id pubmed-4150922
recordtype oai_dc
spelling pubmed-41509222014-09-02 HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells Stanton, Richard J. Prod’homme, Virginie Purbhoo, Marco A. Moore, Melanie Aicheler, Rebecca J. Heinzmann, Marcus Bailer, Susanne M. Haas, Jürgen Antrobus, Robin Weekes, Michael P. Lehner, Paul J. Vojtesek, Borivoj Miners, Kelly L. Man, Stephen Wilkie, Gavin S. Davison, Andrew J. Wang, Eddie C.Y. Tomasec, Peter Wilkinson, Gavin W.G. Article Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix. Cell Press 2014-08-13 /pmc/articles/PMC4150922/ /pubmed/25121749 http://dx.doi.org/10.1016/j.chom.2014.07.005 Text en © 2014 The Authors
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Stanton, Richard J.
Prod’homme, Virginie
Purbhoo, Marco A.
Moore, Melanie
Aicheler, Rebecca J.
Heinzmann, Marcus
Bailer, Susanne M.
Haas, Jürgen
Antrobus, Robin
Weekes, Michael P.
Lehner, Paul J.
Vojtesek, Borivoj
Miners, Kelly L.
Man, Stephen
Wilkie, Gavin S.
Davison, Andrew J.
Wang, Eddie C.Y.
Tomasec, Peter
Wilkinson, Gavin W.G.
spellingShingle Stanton, Richard J.
Prod’homme, Virginie
Purbhoo, Marco A.
Moore, Melanie
Aicheler, Rebecca J.
Heinzmann, Marcus
Bailer, Susanne M.
Haas, Jürgen
Antrobus, Robin
Weekes, Michael P.
Lehner, Paul J.
Vojtesek, Borivoj
Miners, Kelly L.
Man, Stephen
Wilkie, Gavin S.
Davison, Andrew J.
Wang, Eddie C.Y.
Tomasec, Peter
Wilkinson, Gavin W.G.
HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
author_facet Stanton, Richard J.
Prod’homme, Virginie
Purbhoo, Marco A.
Moore, Melanie
Aicheler, Rebecca J.
Heinzmann, Marcus
Bailer, Susanne M.
Haas, Jürgen
Antrobus, Robin
Weekes, Michael P.
Lehner, Paul J.
Vojtesek, Borivoj
Miners, Kelly L.
Man, Stephen
Wilkie, Gavin S.
Davison, Andrew J.
Wang, Eddie C.Y.
Tomasec, Peter
Wilkinson, Gavin W.G.
author_sort Stanton, Richard J.
title HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
title_short HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
title_full HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
title_fullStr HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
title_full_unstemmed HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells
title_sort hcmv pul135 remodels the actin cytoskeleton to impair immune recognition of infected cells
description Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix.
publisher Cell Press
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150922/
_version_ 1613129885520232448

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