title: Human adenovirus 52 uses sialic acid-containing glycoproteins and the coxsackie and adenovirus receptor for binding to target cells.
abstract: 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.
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Annasara
authors: A
authors: Lenman
authors: University of Tübingen, Interfaculty Institute of Biochemistry, Tübingen, Germany.
authors: A Manuel
authors: AM
authors: Liaci
authors: Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Yan
authors: Y
authors: Liu
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Carin
authors: C
authors: Årdahl
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Anandi
authors: A
authors: Rajan
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Emma
authors: E
authors: Nilsson
authors: University of Tübingen, Interfaculty Institute of Biochemistry, Tübingen, Germany.
authors: Will
authors: W
authors: Bradford
authors: University of Tübingen, Interfaculty Institute of Biochemistry, Tübingen, Germany.
authors: Lisa
authors: L
authors: Kaeshammer
authors: Division of Infectious Diseases, Naval Medical Center, San Diego, California, United States of America.
authors: Morris S
authors: MS
authors: Jones
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Lars
authors: L
authors: Frängsmyr
authors: Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Ten
authors: T
authors: Feizi
authors: University of Tübingen, Interfaculty Institute of Biochemistry, Tübingen, Germany; Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Thilo
authors: T
authors: Stehle
authors: Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Niklas
authors: N
authors: Arnberg
mesh_terms: D000260:Adenoviruses, Human / Q000737:chemistry / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D056189:Viral Tropism / Q000502:physiology*; D053585:Virus Attachment
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006023:Glycoproteins; D014764:Viral Proteins