TY - JOUR
T1 - Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure
AU - Burckhardt, Christoph J.
AU - Suomalainen, Maarit
AU - Schoenenberger, Philipp
AU - Boucke, Karin
AU - Hemmi, Silvio
AU - Greber, Urs F.
N1 - Funding Information:
We thank Curzio Rüegg (University of Lausanne) for integrin-Fc constructs; Bernhard Wehrle-Haller (University Hospital of Geneva) for the actin-EGFP construct; Mark McNiven (Mayo Clinic, Rochester, USA) for Dyn2-EGFP; and Jeff Bergelson (The Children's Hospital of Philadelphia, USA) for CAR, CAR-GPI, and CAR-tailless constructs. We thank Urs Ziegler (Center for Microscopy and Image Analysis, University of Zurich) for instructions concerning FRAP measurements; Stefan Schauer (Functional Genomics Center, University of Zurich), Trinh Hung Viet, Andreas Jurgeit, and Leta Fuchs (Institute of Molecular Life Sciences, University of Zurich) for Biacore support; high-throughput image-based data acquisition or purifying soluble integrins; and Ari Helenius and Helge Ewers (ETH Zurich) for access and introduction to TIRF microscopy. The work was supported by grants from the Swiss National Science Foundation, the Swiss SystemsX.ch initiative, grant LipidX-2008/011, and the Novartis Research Foundation (to U.F.G.). C.J.B. and U.F.G. initiated the study, and U.F.G. coordinated the study. C.J.B., M.S., P.S., S.H., and U.F.G. designed experiments. C.J.B. performed most experiments, except Figure 1 B (P.S.), Figure 6 (U.F.G. and K.B.), Figures 5 A–5E (K.B.), Figure 7 (M.S.), Figure S6 (M.S.); and C.J.B., P.S., K.B., S.H., M.S., and U.F.G. analyzed experiments. S.H. provided essential reagents. C.J.B., M.S., and U.F.G. wrote the manuscript.
PY - 2011/8/18
Y1 - 2011/8/18
N2 - Viral particle binding to plasma membrane receptors elicits virus motions, recruits signaling proteins, and triggers membrane bending and fission, finally resulting in endocytic virus uptake. Here we analyze how human adenovirus engages its receptor coxsackievirus adenovirus receptor (CAR) and coreceptor αv integrin to move on the plasma membrane. Virus binding to CAR through fiber knobs gave rise to diffusive motions and actomyosin-2-dependent drifts, while integrin-targeted viruses were spatially more confined. Diffusions, drifts, and confined motions were specifically observed with viral particles that were subsequently internalized. CAR-mediated drifts together with integrin binding supported fiber shedding from adenovirus particles, leading to exposure of the membrane-lytic internal virion protein VI and enhanced viral escape from endosomes. Our results show that adenovirus uncoating is initiated at the plasma membrane by CAR drifting motion and binding to immobile integrins.
AB - Viral particle binding to plasma membrane receptors elicits virus motions, recruits signaling proteins, and triggers membrane bending and fission, finally resulting in endocytic virus uptake. Here we analyze how human adenovirus engages its receptor coxsackievirus adenovirus receptor (CAR) and coreceptor αv integrin to move on the plasma membrane. Virus binding to CAR through fiber knobs gave rise to diffusive motions and actomyosin-2-dependent drifts, while integrin-targeted viruses were spatially more confined. Diffusions, drifts, and confined motions were specifically observed with viral particles that were subsequently internalized. CAR-mediated drifts together with integrin binding supported fiber shedding from adenovirus particles, leading to exposure of the membrane-lytic internal virion protein VI and enhanced viral escape from endosomes. Our results show that adenovirus uncoating is initiated at the plasma membrane by CAR drifting motion and binding to immobile integrins.
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U2 - 10.1016/j.chom.2011.07.006
DO - 10.1016/j.chom.2011.07.006
M3 - Article
C2 - 21843868
AN - SCOPUS:80051887181
SN - 1931-3128
VL - 10
SP - 105
EP - 117
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -