Novel, soluble isoform of the herpes simplex virus (HSV) receptor nectin1 (or PRR1-HIgR-HveC) modulates positively and negatively susceptibility to HSV infection

A novel member of the nectin family, nectin1 gamma, was molecularly cloned. The cDNA has the same ectodomain as nectin1 alpha and nectin1 beta, the tw o known transmembrane isoforms that serve as receptors for herpes simplex v irus (HSV) entry into human cell lines (nectin1 alpha and nectin1 beta, als o railed PRR1-HveC and HIgR, respectively). The 1.4-kb transcript, which or iginated by alternative splicing, is expressed in human cell lines, and app ears to have a narrow distribution in human tissues. The sequence does not have a hydrophobic anchoring region, and the protein is secreted in the cul ture medium of cells transfected with the cDNA, Nectin1 gamma, purified fro m culture medium, can compete with membrane-bound nectin1 beta and reduce H SV infectivity, The expression of nectin1 gamma cDNA in cells resistant to HSV infection and lacking HSV receptors enables HSV to enter the cell, whic h implies that it is present at the cell surface, Thus, nectin1 gamma has t he potential both to mediate and to reduce HSV entry into cells.