Measles virus-substance P receptor interactions: Possible novel mechanism of viral fusion

Abstract

Measles virus (MV) encodes the fusion protein (F) that mediates cell fusion and intercellular spread of the virus, and is homologous to the carboxy terminus of the neuropeptide substance P (SP). In addition, the oligopeptide Z-D-Phe-L-Phe-Gly, also homologous to F and SP, inhibits MV fusion with target cells. These observations raise the question of whether MV uses the SP receptor (SPR) during a specific phase of its infectious cycle. In this report, we examine the structural and functional consequences of this interaction and show, using cross-linking studies, that MV and SP specifically bind to a 52-58-kD protein, previously reported to comprise the SPR on human IM-9 lymphoblasts. Moreover, bound MV and SP are shown to reciprocally displace each other from these cells. In addition, we demonstrate that anti-SP antisera inhibits the cell-to-cell spread of MV, and that SP blocks MV fusion with target cells. These results indicate the presence of MV-SPR interactions during viral fusion, and suggest possible novel mechanisms for viral entry into cells.