A Molecular Mechanism of the Fusion Reaction between HVJ (Sendai virus) Envelope and Erythrocyte Membrane

Abstract

A Molecular mechanism of the fusion reaction between HVJ enevelope and erythrocyte membrane was studied. N-terminal domain of the F_1 subunit of F(fusion) protein was assigned to the fusogenic domain from results of several experiments including limited digestion with protease, surface labeling, and photo-crosslinking. This domain is exposed on the protein surface despite its hydrophobicity, and closely opposed to cell membranes when the virion bound to the target surface. Comparison of amino acid sequences of the fusogenic domains found in F (or F-like) protein of paramyxoviruses with other hydrophobic sequences, such as signal peptides and transmembrane sequences, revealed that only fusogenic domains maintain very high homology of amino acid sequences. A hypothesis that some membrane components might bind to the domain and cause membrane fusion was thus proposed. Experimental tests of this hypothesis revealed a temperature-dependent binding of cholesterol to F protein. Evidence supporting the notion that the fusogenic domain is the binding site of cholesterol was obtained. Furthermore, peptides with inhibitory activity against the fusion reaction and infection were shown to bind to the fusogenic domain of F protein and to hamper cholesterol binding. Thus, the binding of cholesterol in the target membrane with the N-terminal portion of the F_1 subnit seems to be an important step in the fusion reaction.