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Publication Abstract from PubMed

Adeno-associated virus 9 (AAV9) has enhanced capsid-associated tropism for cardiac muscle and the ability to cross the blood brain barrier compared to other AAV serotypes. To help identify the structural features facilitating these properties, we have used cryo-electron microscopy (cryo-EM) and three-dimensional image reconstruction (cryo-reconstruction) and X-ray crystallography to determine the structure of the AAV9 capsid at 9.7 and 2.8-A resolution, respectively. The AAV9 capsid exhibits the surface topology conserved in all AAVs: depressions at each icosahedral twofold symmetry axis and surrounding each fivefold axis, three separate protrusions surrounding each threefold axis, and a channel at each fivefold axis. The AAV9 viral protein (VP) has a conserved core structure, consisting of an eight-stranded, beta-barrel motif and the alphaA helix, which are present in all parvovirus structures. The AAV9 VP differs in nine variable surface regions (VRs I to IX) when compared to AAV4, but at only three (VR-I, VR-II, and VR-IV) compared to AAV2 and AAV8. VR-I differences modify the raised region of the capsid surface between the twofold and fivefold depressions. The VR-IV difference produces smaller threefold protrusions in AAV9 that are less "pointed" compared to AAV2 and AAV8. Significantly, residues in the AAV9 VRs have been identified as important determinants of cellular tropism and transduction and dictate its antigenic diversity from AAV2. Hence, the AAV9 VRs likely confer the unique infection phenotypes of this serotype.

Structural insight into the unique properties of Adeno-Associated Virus Serotype 9.,Dimattia MA, Nam HJ, Van Vliet K, Mitchell M, Bennett A, Gurda BL, McKenna R, Olson NH, Sinkovits RS, Potter M, Byrne BJ, Aslanidi G, Zolotukhin S, Muzyczka N, Baker TS, Agbandje-McKenna M J Virol. 2012 Apr 11. PMID:22496238^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.