Artificial extension of the adenovirus fiber shaft inhibits infectivity in coxsackievirus and adenovirus receptor-positive cell lines.
Recent studies demonstrate that virus-cellular receptor interactions are not the sole determinants of adenovirus (Ad) tropism. It has been shown that the fiber shaft length, which ranges from 6 to 23 beta-repeats in human Ads, also influences viral tropism. However, there is no report that investigates whether artificial extension of the shaft alters the infectivity profile of Ad. Therefore, we constructed Ad serotype 5 (Ad5) capsid-based longer-shafted Ad vectors by incorporating Ad2 shaft fragments of different lengths into the Ad5 shaft. We show that "longer-shafted" Ad vectors (up to 32 beta-repeats) could be rescued. We also show that longer-shafted Ad vectors had no impact on knob-CAR (coxsackievirus and Ad receptor) interaction compared to wild-type Ad. Nevertheless, gene transfer efficiencies of longer-shafted Ad vectors were lower in CAR-positive cell lines compared to wild-type Ad. We suggest that artificial extension of the shaft can inhibit infectivity in the context of CAR-positive cell lines without modification of knob-CAR interaction.
Seki
Toshiro
T
Division of Human Gene Therapy, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
Dmitriev
Igor
I
Kashentseva
Elena
E
Takayama
Koichi
K
Rots
Marianne
M
Suzuki
Kaori
K
Curiel
David T
DT
D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D002213:Capsid / Q000235:genetics* / Q000378:metabolism; D036022:Capsid Proteins; D002461:Cell Line, Transformed; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004770:Enterovirus / Q000235:genetics / Q000378:metabolism*; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C018315:hexon capsid protein, Adenovirus