Enhanced transduction of CAR-negative cells by protein IX-gene deleted adenovirus 5 vectors.
In human adenoviruses (HAdV), 240 copies of the 14.3-kDa minor capsid protein IX stabilize the capsid. Three N-terminal domains of protein IX form triskelions between hexon capsomers. The C-terminal domains of four protein IX monomers associate near the facet periphery. The precise biological role of protein IX remains enigmatic. Here we show that deletion of the protein IX gene from a HAdV-5 vector enhanced the reporter gene delivery 5 to 25-fold, specifically to Coxsackie and Adenovirus Receptor (CAR)-negative cell lines. Deletion of the protein IX gene also resulted in enhanced activation of peripheral blood mononuclear cells. The mechanism for the enhanced transduction is obscure. No differences in fiber loading, integrin-dependency of transduction, or factor-X binding could be established between protein IX-containing and protein IX-deficient particles. Our data suggest that protein IX can affect the cell tropism of HAdV-5, and may function to dampen the innate immune responses against HAdV particles.
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. R.C.Hoeben@lumc.nl
Jeroen
J
de Vrij
Sanne K
SK
van den Hengel
Taco G
TG
Uil
Danijela
D
Koppers-Lalic
Iris J C
IJ
Dautzenberg
Oscar M J A
OM
Stassen
Montserrat
M
Bárcena
Masato
M
Yamamoto
Corrina M A
CM
de Ridder
Robert
R
Kraaij
Kitty M
KM
Kwappenberg
Marco W
MW
Schilham
Rob C
RC
Hoeben
D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D036022:Capsid Proteins; D016023:Integrins; D011991:Receptors, Virus