3D structure of canine adenovirus serotype 2 capsid

Unit for Virus Host Cell Interaction, UMR 5233, Université Joseph Fourier-EMBL-CNRS, Grenoble, France; Institut de Biologie Structurale Jean-Pierre Ebel, UMR5075 CEA-CNRS-UJF, Grenoble France; Institut de Génétique Moléculaire de Montpellier, CNRS 5535, Montpellier, France; Universités Montpellier I and II, Montpellier, France; Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA; Centre de Recherche de Biochimie Macromoléculaire, UMR 5237 CNRS-Universités Montpellier I and II, Montpellier, France

^* To whom correspondence should be addressed. Email: schoehn{at}embl.fr. eric.kremer{at}igmm.cnrs.fr.

	Abstract

There are more than 100 known adenovirus serotypes, including 50 human serotypes. Because adenovirus-induced disease is relatively species-specific, vectors derived from nonhuman serotypes may have wider clinical potential based, in part, on the lack of ubiquitous memory immunity. Whereas a few of the human serotype capsids have been studied at the structural level, none of the nonhuman serotypes have been analysed. The basis laid by the analysis of human adenovirus has allowed us to determine and compare the 3D structure of the capsid of canine serotype 2 (CAV-2) to that of HAdV-5. We show that CAV-2 capsid has a smoother structure than the human serotypes. Many of the external loops found in the HAdV-5 penton base and the hexon, against which the antibody response is directed, are shorter or absent in CAV-2. On the other hand, the CAV-2 fibre appears to be more complex, with two bends in the shaft. An interesting difference between the human and dog viruses is that the C-terminal part of protein IX is in a different position, making an antenna sticking out of the CAV-2 capsid. The comparison between the two viruses allows the identification of sites that should be easy to modify on the CAV-2 capsid for altering tissue tropism or other biological activities.