Heparan sulfate proteoglycan mediates the selective attachment and internalization of serotype 3 human adenovirus dodecahedron.

Romain R Vivès (1) , Hugues Lortat-Jacob (1) , Jadwiga Chroboczek (1) , Pascal Fender (2)

1 IBS - UMR 5075 - Institut de biologie structurale
2 UVHCI - Unit of Virus Host Cell Interactions = Biologie structurale des interactions entre virus et cellule hôte

During adenovirus type 3 (Ad3) infection cycle, the penton (Pt) of the viral capsid, a noncovalent complex of fiber and penton base proteins, is produced in large excess and self-assembles to form a highly organized dodecahedral structure, termed dodecahedron (Dd). The physiological role of these particles is poorly understood, but we have recently reported that they can penetrate cells with high efficiency and thus may constitute an attractive tool for gene or protein delivery approaches. Surprisingly, Dd displayed the ability to enter cells non-permissive to Ad3, suggesting the existence of additional internalization modes. In this study, we show that Ad3 Dd binds to cell surface heparan sulfate (HS) through high affinity interaction with the penton base. Furthermore, binding to HS was found to be the prerequisite for a novel and Dd specific entry pathway that could not be used by Ad3. Overall, these data provide new insights in the possible role of Dd during viral infection and potential therapeutic applications.

Domaines: Biochimie, Biologie Moléculaire

Romain R Vivès, Hugues Lortat-Jacob, Jadwiga Chroboczek, Pascal Fender. Heparan sulfate proteoglycan mediates the selective attachment and internalization of serotype 3 human adenovirus dodecahedron.. Virology, 2004, 321 (2), pp.332-40. ⟨10.1016/j.virol.2004.01.015⟩. ⟨hal-01061438⟩