The spike (S) protein of mouse hepatitis virus (MHV), composed of S1 and S2 subunits, is a component of the spike on the virion surface and has two important biological functions for the virus. It plays a crucial role in virus binding to the MHV receptor and subsequent virus-cell fusion. The outer sub-unit S1 is responsible for binding to the MHV receptor and membrane-anchored S2 subunit may play a major role in virus entry, though the detailed mechanisms underlying these events are not fully understood. It has been also suggested that the S protein is very important as a determinant of viral virulence, since the interaction of S protein with the MHV receptor could determine the outcome of the infection.