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Adeno-Associated Virus pp 47–92Cite as

AAV Capsid Structure and Cell Interactions

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 807))

Abstract

The Adeno-associated viruses (AAVs) are not associated with any diseases, and their ability to package non-genomic DNA and to transduce different cell/tissue populations has generated significant interest in understanding their basic biology in efforts to improve their utilization for corrective gene delivery. This includes their capsid structure, cellular tropism and interactions for entry, uncoating, replication, DNA packaging, capsid assembly, and antibody neutralization. The human and nonhuman primate AAVs are clustered into serologically distinct genetic clade and serotype groups, which have distinct cellular/tissue tropisms and transduction efficiencies. These properties are highly dependent upon the AAV capsid amino acid sequence, their capsid structure, and their interactions with host cell factors, including cell surface receptors, co-receptors, signaling molecules, proteins involved in host DNA replication, and host-derived antibodies. This chapter reviews the current structural information on AAV capsids and the capsid viral protein regions playing a role in the cellular interactions conferring an infective phenotype, which are then used to annotate the functional regions of the capsid. Based on the current data, the indication is that the AAVs, like other members of the Parvoviridae and other ssDNA viruses that form a T = 1 capsid, have evolved a multifunctional capsid with conserved core regions as is required for efficient capsid trafficking, capsid assembly, and genome packaging. Disparate surface loop structures confer differential receptor recognition and are involved in antibody recognition. The role of structural regions in capsid uncoating remains to be elucidated.

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Acknowledgments

The authors would like to thank Lakshmanan Govindasamy and Brittney L. Gurda for help in generating Figures 1–5, Antonette Bennett for providing information on baculovirus expression of AAV VLPs, and Britta Gerlach and Bettina Böttcher for providing unpublished data. NIH project R01 GM082946 to MA-M is also acknowledged for support.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA

    Mavis Agbandje-McKenna

  2. German Cancer Research Center, Heidelberg, Germany

    Jürgen Kleinschmidt

Authors
  1. Mavis Agbandje-McKenna
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  2. Jürgen Kleinschmidt
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Correspondence to Mavis Agbandje-McKenna .

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Editors and Affiliations

  1. Center of Excellence for Regenerative, Health Biotechnology (CERHB), University of Florida, Innovation Drive 13706, Alachua, 32615, Florida, USA

    Richard O. Snyder

  2. INSERM U649, Labo. Thérapie Génique, CHU Hôtel Dieu, bd. Jean Monnet 30, Nantes CX 1, 44035, France

    Philippe Moullier

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Agbandje-McKenna, M., Kleinschmidt, J. (2012). AAV Capsid Structure and Cell Interactions. In: Snyder, R., Moullier, P. (eds) Adeno-Associated Virus. Methods in Molecular Biology, vol 807. Humana Press. https://doi.org/10.1007/978-1-61779-370-7_3

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  • DOI: https://doi.org/10.1007/978-1-61779-370-7_3

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  • Print ISBN: 978-1-61779-369-1

  • Online ISBN: 978-1-61779-370-7

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