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Journal of Virology, June 2001, p. 5375-5380, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5375-5380.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Structural Analysis of a Fiber-Pseudotyped Adenovirus with Ocular Tropism Suggests Differential Modes of Cell Receptor Interactions

Charles Y. Chiu,1 Eugene Wu,2 Swati L. Brown,2 Dan J. Von Seggern,2 Glen R. Nemerow,2,* and Phoebe L. Stewart1,*

Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, California 90095,1 and Department of Immunology, The Scripps Research Institute, La Jolla, California 920372

Received 1 November 2000/Accepted 26 February 2001

Adenovirus (Ad) entry into cells is initiated by the binding of the fiber knob to a cell surface receptor. The coxsackie- and adenovirus receptor (CAR) functions as the attachment receptor for many, but not all, Ad serotypes. Ad type 37 (Ad37), a subgroup D virus that causes keratoconjunctivitis in humans, does not infect cells via CAR despite demonstrated binding of the Ad37 knob to CAR. We have pseudotyped a fiber deletion Ad5 vector with the Ad37 fiber (Ad37f), and this vector retains the ocular tropism of Ad37. Here we present a cryo-electron microscopy reconstruction of Ad37f that shows the entire Ad37 fiber, including the shaft and knob domains. We have previously proposed that Ad37 may not utilize CAR for cell entry because of the geometric constraints imposed by a rigid fiber (E. Wu, J. Fernandez, S. K. Fleck, D. Von Seggern, S. Huang, and G. R. Nemerow, Virology 279:78-89, 2001). Consistent with this hypothesis, our structural results show that the Ad37 fiber is straight and rigid. Modeling of the interaction between Ad37f and host cell receptors indicates that fiber flexibility or rigidity, as well as length, can affect receptor usage and cellular tropism.

* Corresponding author. Mailing address for Phoebe L. Stewart: Department of Molecular and Medical Pharmacology, UCLA School of Medicine, A-324 CIMI, Box 951770, Los Angeles, CA 90095-1770. Phone: (310) 206-7055. Fax: (310) 206-8975. E-mail: pstewart{at}mednet.ucla.edu. Mailing address for Glen R. Nemerow: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037. Phone: (858) 784-8072. Fax: (858) 784-8472. E-mail: gnemerow{at}scripps.edu.

Journal of Virology, June 2001, p. 5375-5380, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5375-5380.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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