Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulatedin dilated cardiomyopathy - Implications for cardiotropic viral infections
M. Noutsias et al., Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulatedin dilated cardiomyopathy - Implications for cardiotropic viral infections, CIRCULATION, 104(3), 2001, pp. 275-280
Citations number
31
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background - The coxsackievirus and adenovirus receptor (CAR) was identifie
d as a common cellular receptor for both viruses, but its biological and pa
thogenic relevance is uncertain. Knowledge of CAR localization in the human
cardiovascular system is limited but important with respect to CAR-depende
nt viral infections and gene transfer using CAR-dependent viral vectors.
Methods and Results - Explanted failing hearts from 13 patients (8 with dil
ated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM]) and no
rmal donor hearts (n=7) were investigated for the expression levels and sub
cellular localization of CAR and the adenovirus coreceptors alpha (v)beta (
3) and alpha (v)beta (3) integrins, CAR immunoreactivity was very low in no
rmal and non-DCM hearts, whereas strong CAR signals occurred at the interca
lated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%); these strong s
ignals colocalized with both integrins. In all hearts, CAR was detectable i
n subendothelial layers of the vessel wall, but not on the luminal endothel
ial surface, and on interstitial cells. Human CAR (hCAR) expressed in rat c
ardiomyocytes was targeted to cell-cell contacts, which resembled CAR local
ization in DCM hearts and resulted in 15-fold increased adenovirus uptake.
Conclusions - Low hCAR abundance may render normal human myocardium resista
nt to CAR-dependent viruses, whereas re-expression of hCAR, such as that ob
served in DCM, may be a key determinant of cardiac susceptibility to viral
infections. Asymmetric expression of hCAR in the vessel wall may be an impo
rtant determinant of adenovirus tropism in humans. hCAR subcellular localiz
ation in human myocardium and hCAR targeting to cell-cell contacts in cardi
omyocyte cultures suggest that hCAR may play a role in cell-cell contact fo
rmation.