The structure of adeno-associated virus serotype 3B (AAV-3B): Insights into receptor binding and immune evasion

Thomas F. Lerch; Qing Xie; Michael S. Chapman

doi:10.1016/j.virol.2010.03.027

The structure of adeno-associated virus serotype 3B (AAV-3B): Insights into receptor binding and immune evasion

Thomas F. Lerch
, Qing Xie
, Michael S. Chapman

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

Adeno-associated viruses (AAVs) are leading candidate vectors for human gene therapy. AAV serotypes have broad cellular tropism and use a variety of cellular receptors. AAV serotype 3 binds to heparan sulfate proteoglycan prior to cell entry and is serologically distinct from other serotypes. The capsid features that distinguish AAV-3B from other serotypes are poorly understood. The structure of AAV-3B has been determined to 2.6. Å resolution from twinned crystals of an infectious virus. The most distinctive structural features are located in regions implicated in receptor and antibody binding, providing insights into the cell entry mechanisms and antigenic nature of AAVs. We show that AAV-3B has a lower affinity for heparin than AAV-2, which can be rationalized by the distinct features of the AAV-3B capsid. The structure of AAV-3B provides an additional foundation for the future engineering of improved gene therapy vectors with modified receptor binding or antigenic characteristics.

Original language	English (US)
Pages (from-to)	26-36
Number of pages	11
Journal	Virology
Volume	403
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2010.03.027
State	Published - Jul 2010
Externally published	Yes

Funding

The authors would like to thank Thayumanasamy Somasundaram, Weishu Bu, and the staff at CHESS, who helped with data collection. The authors also gratefully acknowledge Heather Ongley, Joan Hare, Omar Davulcu and other members of the Chapman lab for the valuable discussions and comments. CHESS is supported by the NSF and NIH/NIGMS via NSF award DMR-0225180 and the MacCHESS resource is supported by NIH/NCRR award RR-01646 . This research was supported by the National Institutes of Health R01-GM66875 (MSC).

Funders	Funder number
NIH NCRR	RR-01646
NIH/NIGMS	DMR-0225180
Author National Science Foundation National Science Foundation National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health National Science Foundation National Science Foundation
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Institute of General Medical Sciences	R01GM066875

Keywords

Antibody
Crystal
Gene therapy
Heparan sulfate
Heparin
Parvovirus
Vector

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2010.03.027

Cite this

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title = "The structure of adeno-associated virus serotype 3B (AAV-3B): Insights into receptor binding and immune evasion",

abstract = "Adeno-associated viruses (AAVs) are leading candidate vectors for human gene therapy. AAV serotypes have broad cellular tropism and use a variety of cellular receptors. AAV serotype 3 binds to heparan sulfate proteoglycan prior to cell entry and is serologically distinct from other serotypes. The capsid features that distinguish AAV-3B from other serotypes are poorly understood. The structure of AAV-3B has been determined to 2.6. {\AA} resolution from twinned crystals of an infectious virus. The most distinctive structural features are located in regions implicated in receptor and antibody binding, providing insights into the cell entry mechanisms and antigenic nature of AAVs. We show that AAV-3B has a lower affinity for heparin than AAV-2, which can be rationalized by the distinct features of the AAV-3B capsid. The structure of AAV-3B provides an additional foundation for the future engineering of improved gene therapy vectors with modified receptor binding or antigenic characteristics.",

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note = "Funding Information: The authors would like to thank Thayumanasamy Somasundaram, Weishu Bu, and the staff at CHESS, who helped with data collection. The authors also gratefully acknowledge Heather Ongley, Joan Hare, Omar Davulcu and other members of the Chapman lab for the valuable discussions and comments. CHESS is supported by the NSF and NIH/NIGMS via NSF award DMR-0225180 and the MacCHESS resource is supported by NIH/NCRR award RR-01646 . This research was supported by the National Institutes of Health R01-GM66875 (MSC). ",

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The structure of adeno-associated virus serotype 3B (AAV-3B): Insights into receptor binding and immune evasion

Abstract

Funding

Keywords

ASJC Scopus subject areas

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