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Journal of Virology, November 2000, p. 10639-10649, Vol. 74, No. 22
Généthon III and CNRS URA 1923,
Evry,1 and Laboratoire de Virologie & Pathogénèse Virale, CNRS UMR 5537, Lyon,2 France, and Division of
Immunologic and Infectious Diseases, Children's Hospital of
Philadelphia, Philadelphia, Pennsylvania3
Received 1 May 2000/Accepted 21 August 2000
The best-characterized receptors for adenoviruses (Ads) are the
coxsackievirus-Ad receptor (CAR) and integrins
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Canine Adenovirus Type 2 Attachment and
Internalization: Coxsackievirus-Adenovirus Receptor, Alternative
Receptors, and an RGD-Independent Pathway
v
5 and
v
3, which facilitate entry. The
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
M
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
v
5 and
v
3
integrins. Our results demonstrate that CAV-2 transduction is augmented
by CAR and possibly by
v
5, though
transduction can be CAR and
v
3/5
independent but is
M
2, MHC-I, and RGD
independent, demonstrating a transduction mechanism which is distinct
from that of Ad2/5.
*
Corresponding author. Mailing address:
Généthon III/CNRS URA 1923, 1bis, rue de l'Internationale,
91002 Evry, France. Phone: 33 (0) 1-69-47-10-30. Fax: 33 (0)
1-69-47-28-38. E-mail: ekremer{at}genethon.fr.
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