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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,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
 NLK 
   
      Cell Press Free Archives
   
    od 2007-03-15 do Před 1 rokem
   
      Free Medical Journals
   
    od 2007 do Před 1 rokem
    
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- buňky NK imunologie virologie MeSH
- CD8-pozitivní T-lymfocyty imunologie virologie MeSH
- Cytomegalovirus imunologie MeSH
- cytoskeletální proteiny metabolismus MeSH
- imunologické synapse virologie MeSH
- imunomodulace MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- mikrofilamenta metabolismus MeSH
- rodina proteinů Wiskottova-Aldrichova syndromu metabolismus MeSH
- talin metabolismus MeSH
- virové proteiny fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
Citace poskytuje Crossref.org
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- $a 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.
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