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 - Summary 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 U L/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 - Summary 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 U L/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.
UR - http://www.scopus.com/inward/record.url?scp=84909580979&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2014.07.005
DO - 10.1016/j.chom.2014.07.005
M3 - Article
C2 - 25121749
AN - SCOPUS:84909580979
SN - 1931-3128
VL - 16
SP - 201
EP - 214
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -