Adenovirus 11p downregulates CD46 early in infection.
Adenovirus 11 prototype (Ad11p), belonging to species B, uses CD46 as an attachment receptor. CD46, a complement regulatory molecule, is expressed on all human nucleated cells. We show here that Ad11p virions downregulate CD46 on the surface of K562 cells as early as 5min p.i. Specific binding to CD46 by the Ad11p fiber knob was required to mediate downregulation. The complement regulatory factors CD55 and CD59 were also reduced to a significant extent as a consequence of Ad11p binding to K562 cells. In contrast, binding of Ad7p did not result in downregulation of CD46 early in infection. Thus, the presumed interaction between Ad7p and CD46 did not have the same consequences as the Ad11p-CD46 interaction, the latter virus (Ad11p) being a promising gene therapy vector candidate. These findings may lead to a better understanding of the pathogenesis of species B adenovirus infections.
Gustafsson
Dan J
DJ
Department of Clinical Microbiology, Virology, Umeå University, SE-901 85 Umeå, Sweden.
Andersson
Emma K
EK
Hu
Yan-Ling
YL
Marttila
Marko
M
Lindman
Kristina
K
Strand
Mårten
M
Wang
Li
L
Mei
Ya-Fang
YF
D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000821:virology; D005822:Genetic Vectors; D006801:Humans; D020014:K562 Cells / Q000821:virology; D008168:Lung / Q000166:cytology / Q000821:virology; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
D018958:CD55 Antigens; D018957:CD59 Antigens; D036022:Capsid Proteins; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus