CARDIOVIRULENT COXSACKIEVIRUSES AND THE DECAY-ACCELERATING FACTOR (CD55) RECEPTOR

Group B coxsackieviruses are etiologically linked with many human dise ases including acute myocarditis and associated chronic dilated cardio myopathy. Well-established CVB3 cardiovirulent strains (CVB3c((s))) wi th known phenotypic differences have been used to study the pathogenes is of virus-induced heart disease. The receptor-binding characteristic s of cardiovirulent CVB3 are not known, but may represent one mechanis m accounting for differences in disease virulence. In this study, inte ractions between CVB3c((s)) and the decay-accelerating factor (DAF or CD55) cell surface receptor were examined. Anti-DAF monoclonal antibod ies (MAbs) blocked virus binding and infection of susceptible HeLa cel ls. Virus binding was significantly reduced by treatment of these cell s with phosphatidylinositol phospholipase C enzyme, which rendered the m DAF-deficient CVB3c((s)) exhibited a differential propensity for the DAF receptor, as several cardiovirulent strains interacted more stron gly than others. However, virus binding and infection was always most effectively blocked by MAbs directed against the SCR 2 and 3 domains o f DAF, suggesting that binding occurs at a similar site(s) on the mole cule for all strains. Virus binding and internalization were associate d with DAF down-regulation at the cell surface, as monitored by flow c ytometry analysis. Cardiovirulent CVB3 did not interact with molecules functionally and/or structurally related to DAF, including CD35, CD46 , Factor H, or C4-binding protein. Adenovirus type 2 (Ad2) does not us e the DAF receptor. However, competitive binding assays between Ad2 an d CVB1-6, CVB3c((s)), anti-DAF MAbs, or DAF-reduced cells indicated th at DAF is associated with Ad2 receptors on the HeLa cell membrane. In summary, this study indicates that DAF is an attachment receptor for c ardiovirulent CVB3 and that DAF interaction may be important in the pa thogenesis of CVB-mediated heart disease. (C) 1998 Academic Press.