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

Richard J Stanton; Virginie Prod'homme; Marco A Purbhoo; Melanie Moore; Rebecca J Aicheler; Marcus Heinzmann; Susanne M Bailer; Jürgen Haas; Robin Antrobus; Michael P Weekes; Paul J Lehner; Borivoj Vojtesek; Kelly L Miners; Stephen Man; Gavin S Wilkie; Andrew J Davison; Eddie C Y Wang; Peter Tomasec; Gavin W G Wilkinson

doi:10.1016/j.chom.2014.07.005

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

Richard J Stanton, Virginie Prod'homme, Marco A Purbhoo, Melanie Moore, Rebecca J Aicheler, Marcus Heinzmann, Susanne M Bailer, Jürgen Haas, Robin Antrobus, Michael P Weekes, Paul J Lehner, Borivoj Vojtesek, Kelly L Miners, Stephen Man, Gavin S Wilkie, Andrew J Davison, Eddie C Y Wang, Peter Tomasec, Gavin W G Wilkinson

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	201-14
Number of pages	14
Journal	Cell Host & Microbe
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.chom.2014.07.005
Publication status	Published - 13 Aug 2014
Externally published	Yes

Keywords / Materials (for Non-textual outputs)

Actin Cytoskeleton
Adaptor Proteins, Signal Transducing
CD8-Positive T-Lymphocytes
Cytomegalovirus
Cytoskeletal Proteins
Host-Pathogen Interactions
Humans
Immunological Synapses
Immunomodulation
Killer Cells, Natural
Talin
Viral Proteins
Wiskott-Aldrich Syndrome Protein Family

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10.1016/j.chom.2014.07.005

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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., & Wilkinson, G. W. G. (2014). HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. Cell Host & Microbe, 16(2), 201-14. https://doi.org/10.1016/j.chom.2014.07.005

@article{c3f2eb12fb5145069dae9daebc37ea27,

title = "HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells",

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.",

keywords = "Actin Cytoskeleton, Adaptor Proteins, Signal Transducing, CD8-Positive T-Lymphocytes, Cytomegalovirus, Cytoskeletal Proteins, Host-Pathogen Interactions, Humans, Immunological Synapses, Immunomodulation, Killer Cells, Natural, Talin, Viral Proteins, Wiskott-Aldrich Syndrome Protein Family",

author = "Stanton, {Richard J} and Virginie Prod'homme and Purbhoo, {Marco A} and Melanie Moore and Aicheler, {Rebecca J} and Marcus Heinzmann and Bailer, {Susanne M} and J{\"u}rgen Haas and Robin Antrobus and Weekes, {Michael P} and Lehner, {Paul J} and Borivoj Vojtesek and Miners, {Kelly L} and Stephen Man and Wilkie, {Gavin S} and Davison, {Andrew J} and Wang, {Eddie C Y} and Peter Tomasec and Wilkinson, {Gavin W G}",

year = "2014",

month = aug,

day = "13",

doi = "10.1016/j.chom.2014.07.005",

language = "English",

volume = "16",

pages = "201--14",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "2",

}

Stanton, RJ, Prod'homme, V, Purbhoo, MA, Moore, M, Aicheler, RJ, Heinzmann, M, Bailer, SM, Haas, J, Antrobus, R, Weekes, MP, Lehner, PJ, Vojtesek, B, Miners, KL, Man, S, Wilkie, GS, Davison, AJ, Wang, ECY, Tomasec, P & Wilkinson, GWG 2014, 'HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells', Cell Host & Microbe, vol. 16, no. 2, pp. 201-14. https://doi.org/10.1016/j.chom.2014.07.005

TY - JOUR

T1 - HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells

AU - Stanton, Richard J

AU - Prod'homme, Virginie

AU - Purbhoo, Marco A

AU - Moore, Melanie

AU - Aicheler, Rebecca J

AU - Heinzmann, Marcus

AU - Bailer, Susanne M

AU - Haas, Jürgen

AU - Antrobus, Robin

AU - Weekes, Michael P

AU - Lehner, Paul J

AU - Vojtesek, Borivoj

AU - Miners, Kelly L

AU - Man, Stephen

AU - Wilkie, Gavin S

AU - Davison, Andrew J

AU - Wang, Eddie C Y

AU - Tomasec, Peter

AU - Wilkinson, Gavin W G

PY - 2014/8/13

Y1 - 2014/8/13

N2 - 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.

AB - 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.

KW - Actin Cytoskeleton

KW - Adaptor Proteins, Signal Transducing

KW - CD8-Positive T-Lymphocytes

KW - Cytomegalovirus

KW - Cytoskeletal Proteins

KW - Host-Pathogen Interactions

KW - Humans

KW - Immunological Synapses

KW - Immunomodulation

KW - Killer Cells, Natural

KW - Talin

KW - Viral Proteins

KW - Wiskott-Aldrich Syndrome Protein Family

U2 - 10.1016/j.chom.2014.07.005

DO - 10.1016/j.chom.2014.07.005

M3 - Article

C2 - 25121749

SN - 1931-3128

VL - 16

SP - 201

EP - 214

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 2

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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