Molecular Characterization of the Heparin-Dependent Transduction Domain on the Capsid of a Novel Adeno-Associated Virus Isolate, AAV(VR-942)

Author:

Schmidt Michael1,Govindasamy Lakshmanan2,Afione Sandra1,Kaludov Nick1,Agbandje-McKenna Mavis2,Chiorini John A.1

Affiliation:

1. Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892

2. Department of Biochemistry and Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida 326101

Abstract

ABSTRACT A new adeno-associated virus (AAV), referred to as AAV(VR-942), has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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