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Glycobiology Advance Access published online on June 23, 2004
Glycobiology, doi:10.1093/glycob/cwh118
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Received March 23, 2004
Revised June 11, 2004
Accepted June 17, 2004

ORIGINAL ARTICLES

Analysis of the interaction of adeno-associated virus and heparan sulfate using atomic force microscopy

Atsuko Negishi 1, Jinghua Chen 2, Douglas McCarty 3, R. Jude Samulski 3, Jian Liu 2, Richard Superfine 4*

1 Curriculum in Applied and Materials Sciences, Program in Cellular and Molecular Biophysics, University of North Carolina, Chapel Hill, NC 27599
2 Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599
3 Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599
4 Department of Physics and Astronomy, University of North Carolina, Chapel Hill, NC 27599

* To whom correspondence should be addressed. E-mail: rsuper{at}physics.unc.edu.


  Abstract

Adeno-associated virus (AAV) has been widely used as a viral vector to deliver genes to animal and human tissues in gene therapy studies. Both AAV-2 and AAV-3 utilize cell surface heparan sulfate, a highly sulfated polysaccharide, as a receptor to establish infections. In this study, we used atomic force microscopy to investigate the interaction of heparan sulfate and AAV. A silicon chip functionalized with heparan sulfate was used as a substrate for binding AAV for AFM analysis. To validate our approach, we found that the binding of AAV-2 to the heparan sulfate-surface was effectively competed by soluble heparan sulfate, suggesting that the binding of AAV-2 to the functionalized surface was specific. In addition, we examined the binding of various AAV serotypes, including AAV-1, AAV-2, AAV-3, and AAV-5, to the heparan sulfate-surface. As expected, only AAV-2 and AAV-3 bound, whereas AAV-1 and AAV-5 did not. This observation was consistent with the previous conclusion that AAV-1 and AAV-5 do not utilize heparan sulfate as a receptor for infection. In conclusion, we developed a novel approach to investigate the interaction of AAV virus with its polysaccharide-based receptor at the level of a single viral particle. Given that heparan sulfates serve as receptor for numerous viruses, this approach has the potential to become a generalized method for studying interactions between the viral particle and heparan sulfate, as well as other virus-cell interactions, and potentially serve as a platform for screening antiviral therapies.


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