Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells

PLoS Pathogens

Morris S. Jones¹  Carin Årdahl²  Anandi Rajan²  Lars Frängsmyr²  Emma Nilsson²  Annasara Lenman²  Ten Feizi³  Yan Liu³  Will Bradford⁴  Thilo Stehle⁴  Lisa Kaeshammer⁴  A. Manuel Liaci⁴  Niklas Arnberg⁵ 

[1] Division of Infectious Diseases, Naval Medical Center, San Diego, California, United States of America;Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden;Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom;University of Tübingen, Interfaculty Institute of Biochemistry, Tübingen, Germany;Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America

关键词: Sialic acids;    Cell binding;    Virions;    Binding analysis;    Vibrio cholerae;    Adenoviruses;    Crystal structure;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1004657

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Most adenoviruses attach to host cells by means of the protruding fiber protein that binds to host cells via the coxsackievirus and adenovirus receptor (CAR) protein. Human adenovirus type 52 (HAdV-52) is one of only three gastroenteritis-causing HAdVs that are equipped with two different fiber proteins, one long and one short. Here we show, by means of virion-cell binding and infection experiments, that HAdV-52 can also attach to host cells via CAR, but most of the binding depends on sialylated glycoproteins. Glycan microarray, flow cytometry, surface plasmon resonance and ELISA analyses reveal that the terminal knob domain of the long fiber (52LFK) binds to CAR, and the knob domain of the short fiber (52SFK) binds to sialylated glycoproteins. X-ray crystallographic analysis of 52SFK in complex with 2-O-methylated sialic acid combined with functional studies of knob mutants revealed a new sialic acid binding site compared to other, known adenovirus:glycan interactions. Our findings shed light on adenovirus biology and may help to improve targeting of adenovirus-based vectors for gene therapy.

【 授权许可】

CC BY