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Journal of Virology, June 2004, p. 6381-6388, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6381-6388.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues

Guangping Gao,1,{dagger} Luk H. Vandenberghe,2,{dagger} Mauricio R. Alvira,1 You Lu,1 Roberto Calcedo,1 Xiangyang Zhou,1 and James M. Wilson1*

Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, and The Wistar Institute, Philadelphia, Pennsylvania 19104,1 Gene Therapy Program, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Louvain, Belgium2

Received 8 December 2003/ Accepted 13 February 2004

The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus. Serologic data suggest that AAV infections are prevalent in humans, although analyses of viruses and viral sequences from clinical samples are extremely limited. Molecular techniques were used in this study to successfully detect endogenous AAV sequences in 18% of all human tissues screened, with the liver and bone marrow being the most predominant sites. Sequence characterization of rescued AAV DNAs indicated a diverse array of molecular forms which segregate into clades whose members share functional and serologic similarities. One of the most predominant human clades is a hybrid of two previously described AAV serotypes, while another clade was found in humans and several species of nonhuman primates, suggesting a cross-species transmission of this virus. These data provide important information regarding the biology of parvoviruses in humans and their use as gene therapy vectors.

* Corresponding author. Mailing address: 204 Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-0819. Fax: (215) 898-6588. E-mail: wilsonjm{at}mail.med.upenn.edu.

{dagger} G.G. and L.H.V. contributed equally to this work.

Journal of Virology, June 2004, p. 6381-6388, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6381-6388.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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