MHVR-Independent Cell-Cell Spread of Mouse Hepatitis Virus Infection Requires Neutral pH Fusion

Abstract
Mouse hepatitis virus (MHV) attaches to susceptible cells through the interaction of MHV spike glycoprotein (S) with cellular receptors of the murine carcinoembryonic antigen (CEA) gene family1,2. Cells that lack murine CEA, including cells that are not of murine origin, are resistant to infection3; binding to MHV receptors appears to be a necessary step in the infection of cells by virions. The presence of murine CEA, however, is not required for cell-cell spread of MHV infection4. Cells that lack a functional MHV receptor can become productively infected through incorporation into MHV-induced syncytia. Syncytium formation is a consequence of spike-mediated cell-cell fusion. In this report, we investigated the role of spike-mediated fusion in receptor-independent, cell-associated spread of MHV infection.