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Cell Host Microbe. 2014 Aug 13;16(2):201-214. doi: 10.1016/j.chom.2014.07.005.

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

Author information

1
Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: stantonrj@cf.ac.uk.
2
Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
3
Section of Hepatology, Department of Medicine, Imperial College London, London, W2 1PG, UK.
4
Ludwig-Maximilians-Universität München, Max von Pettenkofer-Institut, Pettenkoferstrasse 9a, 80336 München, Germany.
5
Ludwig-Maximilians-Universität München, Max von Pettenkofer-Institut, Pettenkoferstrasse 9a, 80336 München, Germany; Biological Interfacial Engineering, University of Stuttgart, Nobelstrasse 12, 70569 Stuttgart, Germany.
6
University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
7
Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 65653 Brno, Czech Republic.
8
Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
9
Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow G11 5JR, UK.
10
Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: wilkinsongw1@cf.ac.uk.

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.

PMID:
25121749
PMCID:
PMC4150922
DOI:
10.1016/j.chom.2014.07.005
[Indexed for MEDLINE]
Free PMC Article

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