title: Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure.
abstract: 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.
authors.affiliation: Institute of Molecular Life Science, University of Zürich, Winterthurerstrasse, Switzerland.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Burckhardt
authors.forename: Maarit
authors.initials: M
authors.lastname: Suomalainen
authors.forename: Philipp
authors.initials: P
authors.lastname: Schoenenberger
authors.forename: Karin
authors.initials: K
authors.lastname: Boucke
authors.forename: Silvio
authors.initials: S
authors.lastname: Hemmi
authors.forename: Urs F
authors.initials: UF
authors.lastname: Greber
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000260:Adenoviruses, Human / Q000378:metabolism / Q000472:pathogenicity*; D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D020285:Cryoelectron Microscopy; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D011554:Pseudopodia / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization; D057074:Virus Release; D057646:Virus Uncoating
chemical_list: D000199:Actins; C568771:CLMP protein, human; C568772:CLMP protein, mouse; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006576:Heterocyclic Compounds, 4 or More Rings; D039564:Integrin alphaV; D011991:Receptors, Virus; C090876:polypeptide VI, adenovirus; C472645:blebbistatin; D000205:Actomyosin