14 Activation Cleavage of Viral Spike Proteins by Host Proteases

Abstract

Endoproteolytic cleavage, usually at arginine residues, is a common posttranslational modification of membrane and secretory proteins on the exocytotic transport route. Such proteins include precursors of peptide hormones, neuropeptides, growth factors, coagulation factors, serum albumin, cell-surface receptors, and adhesion molecules. All of these proteins play important roles in a large variety of different biological processes, and these functions depend on proteolytic cleavage of the proteins (for review, see Barr 1991). The same type of processing has also been observed with many viral membrane proteins (Fig. 1) and, in some instances, proved to be a crucial factor in determining organ and host tropism, spread of infection, and pathogenicity of these viruses.

VIRUSES WITH SPIKE PROTEINS UNDERGOING POSTTRANSLATIONAL PROTEOLYTIC CLEAVAGE
Paramyxoviridae
The concept that proteolytic activation of a viral glycoprotein is an important factor in virus replication was first established with the fusion (F) protein of Sendai virus (Homma and Ohuchi 1973; Scheid and Choppin 1974). Cleavage of this protein results in the exposition of a highly conserved hydrophobic sequence at the amino terminus of the F1 fragment (Fig. 1) (Gething et al. 1978; Scheid et al. 1978) which induces fusion of the viral envelope with the plasma membrane of the target cell, thereby allowing entry of the viral genome into the cytoplasm. Cleavage of F is therefore necessary for virus infectivity. Evidence from various biochemical and biophysical data indicates that the membrane fusion characteristic of paramyxoviruses is driven by a hydrophobic interaction of the F1 amino terminus with the lipid bilayer...