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Journal of Virology, April 2005, p. 5047-5058, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5047-5058.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Structure of Adeno-Associated Virus Type 4

Eric Padron,1,{dagger} Valorie Bowman,2,{dagger} Nikola Kaludov,3,{dagger} Lakshmanan Govindasamy,1 Hazel Levy,1 Phillip Nick,1 Robert McKenna,1 Nicholas Muzyczka,4,5 John A. Chiorini,3 Timothy S. Baker,2 and Mavis Agbandje-McKenna1*

Department of Biochemistry and Molecular Biology,1 Department of Molecular Genetics and Microbiology,4 Powell Gene Therapy Center, College of Medicine, University of Florida, Gainesville, Florida,5 Department of Biological Sciences, Purdue University, West Lafayette, Indiana,2 GTTB, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland3

Received 14 July 2004/ Accepted 17 November 2004

Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy applications due to their ability to transduce different target cells. The need to manipulate AAV capsids for specific tissue delivery has generated interest in understanding their capsid structures. The structure of AAV type 4 (AAV4), one of the most antigenically distinct serotypes, was determined to 13-Å resolution by cryo-electron microscopy and image reconstruction. A pseudoatomic model was built for the AAV4 capsid by use of a structure-based sequence alignment of its major capsid protein, VP3, with that of AAV2, to which AAV4 is 58% identical and constrained by its reconstructed density envelope. The model showed variations in the surface loops that may account for the differences in receptor binding and antigenicity between AAV2 and AAV4. The AAV4 capsid surface topology also shows an unpredicted structural similarity to that of Aleutian mink disease virus and human parvovirus B19, autonomous members of the genus, despite limited sequence homology.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610. Phone: (352) 392-5694. Fax: (352) 392-3422. E-mail: mckenna{at}ufl.edu.

{dagger} E.P., V.B., and N.K. contributed equally to this study.

Journal of Virology, April 2005, p. 5047-5058, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5047-5058.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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