Receptor specificity and receptor-induced conformational changes in mouse hepatitis virus spike glycoprotein.

Abstract

Coronavirus spike (S) glycoproteins bind to specific glycoproteins on host cell membranes that serve as virus receptors. Receptors for S glycoproteins of several coronaviruses have been identified (Dveksler, et al, 1991; Dveksler, et al, 1993; Chen, et al, 1995; Yeager, et al, 1992; Delmas, et al, 1992; Tresnan, et al, 1996; Benbacer, et al, 1997). The specificity of virus/receptor interactions is an important determinant of the species-specificity of Coronavirus infection, and may play a role in the tissue tropism and virulence of Coronavirus diseases (Kolb, et al, 1997; Ballesteros, et al, 1997; Sanchez, et al, 1999). The mechanism of entry has been studied in great detail for several enveloped viruses including influenza A virus, avian leukosis viruses and HIV-1 (Kemble, et al, 1994; Stegmann, et al, 1990; Chen, et al, 1999; Gilbert, et al, 1995; Hernandez and White, 1998; Zhang, et al, 1999; Turner and Summers, 1999). Binding of the spike glycoprotein on the viral envelope to the receptor on the cell membrane may induce specific, pre-programmed conformational changes in the spike protein and/or the receptor that bring together the lipid bilayers of the viral envelope and the cell membrane. A fusion pore is created that expands to permit the entry of the viral nucleocapsid into the cytoplasm, leading to virus infection. This chapter will summarize the specificity of the interactions of murine Coronavirus MHV and mutants of MHV with cellular receptors, and discuss evidence that receptor binding induces a temperature-dependent conformational change in the MHV S glycoprotein that may play a role in virus entry and MHV-induced cell fusion.