The short consensus repeats 1 and 2, not the cytoplasmic domain, of human CD46 are crucial for infection of subgroup B adenovirus serotype 35.
Human CD46 (membrane cofactor protein) has recently been identified to be an attachment receptor for subgroup B adenoviruses (Ads); however, the precise interaction between human CD46 and subgroup B Ads are just beginning to be understood. In this study, to characterize the interaction between human CD46 and subgroup B Ads, varieties of mutant CD46 were tested for their ability to act as a receptor for Ad serotype 35 (Ad35), which belongs to subgroup B. In addition, we determined Ad35 vector-mediated transgene expression and cellular uptake of Ad35 vectors in the presence of a set of anti-CD46 antibodies. Our data demonstrated that the short consensus repeats (SCRs) 1 and 2 in human CD46 are important for interaction with Ad35, whereas the cytoplasmic domain of human CD46 was found not to be required for the function as an Ad35 receptor. Rather, a complete deletion of the cytoplasmic domain of human CD46 increased the transduction efficiencies of Ad35 vectors. This information should help in elucidation of the mechanism of subgroup B Ad infection, as well in the improvement of the subgroup B Ad vectors.
Sakurai
Fuminori
F
Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, 567-0085, Japan.
Murakami
Sayaka
S
Kawabata
Kenji
K
Okada
Naoki
N
Yamamoto
Akira
A
Seya
Tsukasa
T
Hayakawa
Takao
T
Mizuguchi
Hiroyuki
H
D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D051916:Membrane Cofactor Protein / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection
D000911:Antibodies, Monoclonal; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; C085301:adenovirus receptor; D008156:Luciferases