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HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells
RJ. Stanton, V. Prod'homme, MA. Purbhoo, M. Moore, RJ. Aicheler, M. Heinzmann, SM. Bailer, J. Haas, R. Antrobus, MP. Weekes, PJ. Lehner, B. Vojtesek, KL. Miners, S. Man, GS. Wilkie, AJ. Davison, EC. Wang, P. Tomasec, GW. Wilkinson,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Cell Press Free Archives
from 2007-03-15 to 1 year ago
Free Medical Journals
from 2007 to 1 year ago
- MeSH
- Adaptor Proteins, Signal Transducing metabolism MeSH
- Killer Cells, Natural immunology virology MeSH
- CD8-Positive T-Lymphocytes immunology virology MeSH
- Cytomegalovirus immunology MeSH
- Cytoskeletal Proteins metabolism MeSH
- Immunological Synapses virology MeSH
- Immunomodulation MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Actin Cytoskeleton metabolism MeSH
- Wiskott-Aldrich Syndrome Protein Family metabolism MeSH
- Talin metabolism MeSH
- Viral Proteins physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Biological Interfacial Engineering University of Stuttgart Nobelstrasse 12 70569 Stuttgart Germany
Medical Research Council University of Glasgow Centre for Virus Research Glasgow G11 5JR UK
Section of Hepatology Department of Medicine Imperial College London London W2 1PG UK
References provided by Crossref.org
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