Mouse adenovirus type 1 attachment is not mediated by the coxsackie-adenovirus receptor.
Common human adenovirus (Ad) vectors are derived from serotype 2 or 5, which use the coxsackie-adenovirus receptor (CAR) as their primary cell receptor. We investigated the receptor usage of mouse adenovirus type 1 (MAV-1), which in vivo is characterized by a pronounced endothelial cell tropism. Alignment of the fiber knob sequences of MAV-1 and those of CAR-using adenoviruses, revealed that amino acid residues, critical for interaction with CAR, are not conserved in the MAV-1 fiber knob. Attachment of MAV-1 to Chinese hamster ovary (CHO) cells was not increased by stable transfection with mouse CAR, whereas the binding efficiency of Ad2 was 20-fold higher in the mouse CAR-transfectant compared to the wild type cells. Also, purified fiber knob of Ad5, which is interchangeable with the Ad2 fiber knob, did not compete with MAV-1 for receptor binding, indicating that MAV-1 binds to a receptor different from CAR. These results support further exploration of an MAV-1-derived vector as a potential vehicle for gene delivery to cell types which are not efficiently transduced by human adenovirus vectors.
Lenaerts
L
L
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. liesbeth.lenaerts@rega.kuleuven.be
Daelemans
D
D
Geukens
N
N
De Clercq
E
E
Naesens
L
L
D000256:Adenoviridae / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D012333:RNA, Messenger; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins