Localization of regions in CD46 that interact with adenovirus

被引:47
作者
Gaggar, A
Shayakhmetov, DM
Liszewski, MK
Atkinson, JP
Lieber, A
机构
[1] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA
[3] Washington Univ, Sch Med, Dept Rheumatol, St Louis, MO USA
关键词
D O I
10.1128/JVI.79.12.7503-7513.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A variety of pathogens use CD46, a ubiquitously expressed membrane protein that regulates complement activation, as a cellular attachment receptor. While the CD46 binding sites of several pathogens, including measles virus, Neisseria gonorrhea, and human herpesvirus 6, have been described, the region of CD46 responsible for adenovirus binding has not been determined. In this study, we used competition experiments with known CD46 ligands, CD46-specific antibodies, and a set of CD46 mutants to localize the binding domain for the group B adenovirus serotype 35 (Ad35). Our results show that Ad35 competes with measles virus for binding to CD46 but not with complement protein C3b. We further show that this interaction is a protein-protein interaction and that N glycosylations do not critically contribute to infection with Ad35 fiber-containing Ad vectors. Our data demonstrate that the native conformation of the CCP2 domain is crucial for Ad35 binding and that the substitution of amino acids at positions 130 to 135 or 152 to 156 completely abolishes the receptor function of CD46. These regions localize to the same planar face of CD46 and likely form an extended adenovirus binding surface, since no single amino acid substitution within these areas eliminates virus binding. Finally, we demonstrate that the infection with a virus possessing human group B serotype Ad11 fibers is also mediated by the CCP2 domain. This information is important to better characterize the mechanisms of the receptor recognition by adenovirus relative to other pathogens that interact with CD46, and it may help in the design of antiviral therapeutics against adenovirus serotypes that use CD46 as a primary cellular attachment receptor.
引用
收藏
页码:7503 / 7513
页数:11
相关论文
共 55 条
[1]   Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5 [J].
Bergelson, JM ;
Cunningham, JA ;
Droguett, G ;
KurtJones, EA ;
Krithivas, A ;
Hong, JS ;
Horwitz, MS ;
Crowell, RL ;
Finberg, RW .
SCIENCE, 1997, 275 (5304) :1320-1323
[2]   Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR [J].
Bewley, MC ;
Springer, K ;
Zhang, YB ;
Freimuth, P ;
Flanagan, JM .
SCIENCE, 1999, 286 (5444) :1579-1583
[3]   Mapping of the primary binding site of measles virus to its receptor CD46 [J].
Buchholz, CJ ;
Koller, D ;
Devaux, P ;
Mumenthaler, C ;
SchneiderSchaulies, J ;
Braun, W ;
Gerlier, D ;
Cattaneo, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (35) :22072-22079
[4]   Cell entry by measles virus: Long hybrid receptors uncouple binding from membrane fusion [J].
Buchholz, CJ ;
Schneider, U ;
Devaux, P ;
Gerlier, D ;
Cattaneo, R .
JOURNAL OF VIROLOGY, 1996, 70 (06) :3716-3723
[5]   Crystal structure of two CD46 domains reveals an extended measles virus-binding surface [J].
Casasnovas, JM ;
Larvie, M ;
Stehle, T .
EMBO JOURNAL, 1999, 18 (11) :2911-2922
[6]   Four viruses, two bacteria, and one receptor: Membrane cofactor protein (CD46) as pathogens' magnet [J].
Cattaneo, R .
JOURNAL OF VIROLOGY, 2004, 78 (09) :4385-4388
[7]   CHARACTERIZATION OF THE ECHOVIRUS-7 RECEPTOR - DOMAINS OF CD55 CRITICAL FOR VIRUS BINDING [J].
CLARKSON, NA ;
KAUFMAN, R ;
LUBLIN, DM ;
WARD, T ;
PIPKIN, PA ;
MINOR, PD ;
EVANS, DJ ;
ALMOND, JW .
JOURNAL OF VIROLOGY, 1995, 69 (09) :5497-5501
[8]   CD46 short consensus repeats III and IV enhance measles virus binding but impair soluble hemagglutinin binding [J].
Devaux, P ;
Buchholz, CJ ;
Schneider, U ;
Escoffier, C ;
Cattaneo, R ;
Gerlier, D .
JOURNAL OF VIROLOGY, 1997, 71 (05) :4157-4160
[9]   CD46 is a cellular receptor for group B adenoviruses [J].
Gaggar, A ;
Shayakhmetov, DM ;
Lieber, A .
NATURE MEDICINE, 2003, 9 (11) :1408-1412
[10]   Identification of the streptococcal M protein binding site on membrane cofactor protein (CD46) [J].
Giannakis, E ;
Jokiranta, TS ;
Ormsby, RJ ;
Duthy, TG ;
Male, DA ;
Christiansen, D ;
Fischetti, VA ;
Bagley, C ;
Loveland, BE ;
Gordon, DL .
JOURNAL OF IMMUNOLOGY, 2002, 168 (09) :4585-4592