Canine adenovirus type 2 attachment and internalization: coxsackievirus-adenovirus receptor, alternative receptors, and an RGD-independent pathway.

C. Soudais (1) , S. Boutin (1) , Ss Hong (2) , M. Chillon (1) , O. Danos (1) , Jm Bergelson (3) , P. Boulanger (2) , Ej Kremer (1)

1 Généthon
2 VPV - Virologie et pathogenèse virale
3 Division of Immunologic and Infectious Diseases

The best-characterized receptors for adenoviruses (Ads) are the coxsackievirus-Ad receptor (CAR) and integrins alpha(v)beta(5) and alpha(v)beta(3), which facilitate entry. The alpha(v) integrins recognize an Arg-Gly-Asp (RGD) motif found in some extracellular matrix proteins and in the penton base in most human Ads. Using a canine adenovirus type 2 (CAV-2) vector, we found that CHO cells that express CAR but not wild-type CHO cells are susceptible to CAV-2 transduction. Cells expressing alpha(M)beta(2) integrins or major histocompatibility complex class I (MHC-I) molecules but which do not express CAR were not transduced. Binding assays showed that CAV-2 attaches to a recombinant soluble form of CAR and that Ad type 5 (Ad5) fiber, penton base, and an anti-CAR antibody partially blocked attachment. Using fluorescently labeled CAV-2 particles, we found that in some cells nonpermissive for transduction, inhibition was at the point of internalization and not attachment. The transduction efficiency of CAV-2, which lacks an RGD motif, surprisingly mimicked that of Ad5 when tested in cells selectively expressing alpha(v)beta(5) and alpha(v)beta(3) integrins. Our results demonstrate that CAV-2 transduction is augmented by CAR and possibly by alpha(v)beta(5), though transduction can be CAR and alpha(v)beta(3/5) independent but is alpha(M)beta(2), MHC-I, and RGD independent, demonstrating a transduction mechanism which is distinct from that of Ad2/5.

Mots clés: P.H.S; Adenoviruses; Canine/genetics/*pathogenicity/*physiology; Animals; CHO Cells; Cell Line; Cricetinae; Dendritic Cells/metabolism; Dogs; Histocompatibility Antigens Class I/metabolism; Humans; Integrins/*metabolism; Receptors; Immunologic/*metabolism; Peptide/*metabolism; Virus/*metabolism; Research Support; Non-U.S. Gov't; U.S. Gov't; P.H.S.; Transduction; Genetic

Domaines: Virologie

C. Soudais, S. Boutin, Ss Hong, M. Chillon, O. Danos, et al.. Canine adenovirus type 2 attachment and internalization: coxsackievirus-adenovirus receptor, alternative receptors, and an RGD-independent pathway.. 2006. ⟨hal-00116153⟩