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Journal of Virology, August 2001, p. 7210-7214, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7210-7214.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Adenovirus Type 9 Fiber Knob Binds to the Coxsackie B Virus-Adenovirus Receptor (CAR) with Lower Affinity than Fiber Knobs of Other CAR-Binding Adenovirus Serotypes

Ian Kirby,1 Rosemary Lord,1 Elizabeth Davison,1 Thomas J. Wickham,2 Peter W. Roelvink,2 Imre Kovesdi,2 Brian J. Sutton,3 and George Santis1,*

Department of Respiratory Medicine and Allergy, The Guy's, King's College and St. Thomas' Hospitals School of Medicine, Guy's Hospital, London SE1 9RT,1 and The Randall Centre, King's College London, London SE1 1UL,3 United Kingdom, and GenVec, Gaithersburg, Maryland 208782

Received 25 August 2000/Accepted 16 April 2001

The coxsackie B virus and adenovirus (Ad) receptor (CAR) functions as an attachment receptor for multiple Ad serotypes. Here we show that the Ad serotype 9 (Ad9) fiber knob binds to CAR with much reduced affinity compared to the binding by Ad5 and Ad12 fiber knobs as well as the knob of the long fiber of Ad41 (Ad41L). Substitution of Asp222 in Ad9 fiber knob with a lysine that is conserved in Ad5, Ad12, and Ad41L substantially improved Ad9 fiber knob binding to CAR, while the corresponding substitution in Ad5 (Lys442Asp) significantly reduced Ad5 binding. The presence of an aspartic acid residue in Ad9 therefore accounts, at least in part, for the reduced CAR binding affinity of the Ad9 fiber knob. Site-directed mutagenesis of CAR revealed that CAR residues Leu73 and Lys121 and/or Lys123 are critical contact residues, with Tyr80 and Tyr83 being peripherally involved in the binding interaction with the Ad5, Ad9, Ad12, and Ad41L fiber knobs. The overall affinities and the association and dissociation rate constants for wild-type CAR as well as Tyr80 and Tyr83 CAR mutants differed between the serotypes, indicating that their binding modes, although similar, are not identical.

* Corresponding author. Mailing address: Department of Respiratory Medicine & Allergy, The Guy's, King's College and St. Thomas' Hospitals School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, St. Thomas St., London SE1 9RT, United Kingdom. Phone: 44-20-79552758. Fax: 44-20-74038640. E-mail: george.santis{at}kcl.ac.uk.

Journal of Virology, August 2001, p. 7210-7214, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7210-7214.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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