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Journal of Virology, June 2006, p. 5516-5522, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02393-05

Gangliosides Are Essential for Bovine Adeno-Associated Virus Entry

Michael Schmidt and John A. Chiorini*

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

Received 14 November 2005/ Accepted 28 February 2006

Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. We have recently identified a bovine adeno-associated virus (BAAV) that demonstrates unique tropism and transduction activity compared to primate AAVs. To better understand the entry pathway and cell tropism of BAAV, we have characterized the initial cell surface interactions required for transduction with BAAV vectors. Like a number of AAVs, BAAV requires cell surface sialic acid groups for transduction and virus attachment. However, glycosphingolipids (GSLs), not cell surface proteins, were required for vector entry and transduction. Incorporation of gangliosides, ceramide-based glycolipids containing one or more sialic acid groups, into the cytoplasmic cell membranes of GSL-depleted COS cells partially reconstituted BAAV transduction. The dependency of BAAV on gangliosides for transduction was further confirmed by studies with C6 cells, a rat glioma cell line that is deficient in the synthesis of complex gangliosides. C6 cells were resistant to transduction by BAAV. Addition of gangliosides to C6 cells prior to transduction rendered the cells susceptible to transduction by BAAV. Therefore, gangliosides are a likely receptor for BAAV.

* Corresponding author. Mailing address: NIH 10/1N113, 10 Center Dr., MSC1190, Bethesda, MD 20892. Phone: (301) 496-4279. Fax: (301) 402-1228. E-mail: jchiorini{at}dir.nidcr.nih.gov.

Journal of Virology, June 2006, p. 5516-5522, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02393-05




This article has been cited by other articles:

  • Schmidt, M., Govindasamy, L., Afione, S., Kaludov, N., Agbandje-McKenna, M., Chiorini, J. A. (2008). Molecular Characterization of the Heparin-Dependent Transduction Domain on the Capsid of a Novel Adeno-Associated Virus Isolate, AAV(VR-942). J. Virol. 82: 8911-8916 [Abstract] [Full Text]  
  • Schmidt, M., Voutetakis, A., Afione, S., Zheng, C., Mandikian, D., Chiorini, J. A. (2008). Adeno-Associated Virus Type 12 (AAV12): a Novel AAV Serotype with Sialic Acid- and Heparan Sulfate Proteoglycan-Independent Transduction Activity. J. Virol. 82: 1399-1406 [Abstract] [Full Text]  
  • Wu, Z., Miller, E., Agbandje-McKenna, M., Samulski, R. J. (2006). {alpha}2,3 and {alpha}2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6.. J. Virol. 80: 9093-9103 [Abstract] [Full Text]  


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