Cloning and epitope mapping of a functional partial fusion receptor for human cytomegalovirus gH

A cDNA clone encoding a partial putative human cytomegalovirus (HCMV) gH fu sion receptor (CMVFR) was previously identified. In this report, the cDNA s equence of CMVFR was determined and the role of this CMVFR in HCMV/cell fus ion was confirmed by rendering fusion-incompetent MOLT-4 cells susceptible to fusion following transfection with receptor cDNA. Blocking experiments u sing recombinant gH or either of two MAbs (against recombinant gH or purifi ed viral gH:gL) provided additional evidence for the role of gH binding to this protein in virus fusion. An HCMV-binding domain of 12 aa in the middle hydrophilic region of CMVFR was identified by fusion blocking studies usin g synthetic receptor peptides. The 1368 bp cDNA of CMVFR contained a predic ted ORF of 345 aa with two potential membrane-spanning domains and several possible nuclear localization signals. A search of sequence databases indic ated that CMVFR is a novel protein. Further characterization of this cell m embrane protein that confers susceptibility to fusion with the viral envelo pe should provide important information about the mechanism by which HCMV i nfects cells.