CHARACTERIZATION OF THE ECHOVIRUS-7 RECEPTOR - DOMAINS OF CD55 CRITICAL FOR VIRUS BINDING

CD55, of decay-accelerating factor (DAF), is a cell surface glycoprote in which regulates complement activity by accelerating the decay of C3 /C5 convertases. Recently, we and others have established that this mo lecule acts as a cellular receptor for echovirus 7 and related viruses . DAF consists of five domains: four short consensus repeats (SCRs) an d a serine/threonine-rich region, attached to the cell surface by a gl ycosylphosphatidyl inositol anchor. Chinese hamster ovary cells stably transfected with deletion mutants of DAF or DAF-membrane cofactor pro tein recombinants were analyzed for virus binding. The results indicat e that the binding of echovirus 7 to DAF specifically requires SCR2, S CR3, and SCR4. There is also a nonspecific requirement for the S/T-ric h region which probably functions to project the binding region away f rom the cell membrane. The three nonpeptide modifications of DAF, N-li nked glycosylation, O-linked glycosylation, and the glycosylphosphatid yl inositol anchor, are not required for virus binding. The SCRs of me mbrane cofactor protein, the closest known relative of DAF, cannot sub stitute for those of DAF with retention of virus binding activity. The monoclonal antibody used to identify DAF as an echovirus receptor, an d which inhibits binding of the virus (monoclonal antibody 854), binds to SCR3.