HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells

Stanton, R. J. et al. (2014) HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. Cell Host and Microbe, 16(2), pp. 201-214. (doi:10.1016/j.chom.2014.07.005)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkie, Dr Gavin and Davison, Professor Andrew
Authors: Stanton, R. J., Prod’homme, V., Purbhoo, M. A., Moore, M., Aicheler, R. J., Heinzmann, M., Bailer, S. M., Haas, J., Antrobus, R., Weekes, M. P., Lehner, P. J., Vojtesek, B., Miners, K. L., Man, S., Wilkie, G. S., Davison, A. J., Wang, E. C.Y., Tomasec, P., and Wilkinson, G. W.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell Host and Microbe
Publisher:Cell Press
ISSN:1931-3128
ISSN (Online):1934-6069
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Cell Host and Microbe 16(2):201-214
Publisher Policy:Reproduced under a Creative Commons License
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