Adenovirus type 5 substituted with type 11 or 35 fiber structure increases its infectivity to human cells enabling dual gene transfer in CD46-dependent and -independent manners.
Infectivity of adenovirus type 5 (Ad5) to cells depends primarily on its fiber-mediated binding to the coxsackievirus and adenovirus receptor (CAR) on target cells. Down-regulated CAR expression, often found in human tumors, hampered Ad5-mediated gene transfer. Ad 11 and Ad 35, belonging to a subtype B group, use CD46 as their cellular receptors; accordingly, chimeric Ad5 whose fiber structure was substituted with that of the type 11 or 35 (Ad5/11 or Ad5/35) could infect human cells in a different manner from Ad5. We found that Ad5/35 infected human tumors, including pancreatic and breast cancer, and human fibroblasts better than Ad5 and Ad5/11. Infectivity of Ad5/35 to these cells was correlated with that of Ad5/11, but efficacy of Ad5/35- and Ad5/11-mediated transduction was not directly correlated with the expression level of CD46 in the target cells. Infection of human hepatoma cells with measles virus, whose cellular receptor is CD46, down-regulated the CD46 expression and reduced subsequent infectivity of Ad5/35 but not Ad5/11. Infection of Ad5 suppressed subsequent gene transfer by Ad5 but not by Ad5/11 orAd5/35. Likewise infection of Ad5/35 decreased following gene transduction by Ad5/35 and Ad5/11, but to a lesser extent by Ad5. These data collectively showed that combinatory use of Ad5 and the chimeric Ad enables dual gene transfer into target cells and suggest that infectivity of subtype B Ad does not completely depend on CD46 expression and that other receptors possibly influence the infectivity.
Yu
Ling
L
Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
Shimozato
Osamu
O
Li
Quanhai
Q
Kawamura
Kiyoko
K
Ma
Guangyu
G
Namba
Masayoshi
M
Ogawa
Tomoko
T
Kaiho
Ikuo
I
Tagawa
Masatoshi
M
D000258:Adenovirus Infections, Human / Q000821:virology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D015536:Down-Regulation; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D018014:Gene Transfer Techniques; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000821:virology; D051916:Membrane Cofactor Protein / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000821:virology*; D011991:Receptors, Virus / Q000096:biosynthesis / Q000378:metabolism; D014161:Transduction, Genetic
C497857:CD46 protein, human; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus