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PDBsum entry 2wbw
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Structural protein
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PDB id
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2wbw
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References listed in PDB file
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Key reference
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Title
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The cell adhesion molecule "car" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.
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Authors
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E.Seiradake,
D.Henaff,
H.Wodrich,
O.Billet,
M.Perreau,
C.Hippert,
F.Mennechet,
G.Schoehn,
H.Lortat-Jacob,
H.Dreja,
S.Ibanes,
V.Kalatzis,
J.P.Wang,
R.W.Finberg,
S.Cusack,
E.J.Kremer.
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Ref.
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Plos Pathog, 2009,
5,
e1000277.
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PubMed id
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Abstract
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Although it has been known for 50 years that adenoviruses (Ads) interact with
erythrocytes ex vivo, the molecular and structural basis for this interaction,
which has been serendipitously exploited for diagnostic tests, is unknown. In
this study, we characterized the interaction between erythrocytes and unrelated
Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these
serotypes agglutinate human erythrocytes, they use different receptors, have
different tropisms and/or infect different species. Using molecular,
biochemical, structural and transgenic animal-based analyses, we found that the
primary erythrocyte interaction domain for HAd37 is its sialic acid binding
site, while CAV-2 binding depends on at least three factors: electrostatic
interactions, sialic acid binding and, unexpectedly, binding to the
coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that
the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life
and significantly reduced liver infection when a CAR-tropic Ad is injected
intravenously. This study provides i) a molecular and structural rationale for
Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene
transfer and iii) a mechanism that may explain the biodistribution and
pathogenic inconsistencies found between human and animal models.
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