Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

Abstract

Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins. Correspondence

Structures of vesicular stomatitis virus glycoprotein: membrane fusion revisited

“…Thus, reversibility of the low-pH-induced fusogenic transition is not necessary for these proteins. Biochemical, structural and functional properties of rhabdovirus G suggested that it was distinct from both class I and class II viral fusion proteins that had been already described [29,53]. Indeed, the pH-dependent equilibrium between the different states of G, the absence of predicted a-helical coiled-coil motif characteristic of class I viral fusion proteins [40] and the absence of activating cleavage (neither in G nor in an accompanying protein) strongly suggested that G could define a new category of fusogenic glycoproteins.…”

Interferon response following infection with genetically similar isolates of viral haemorrhagic septicaemia virus (VHSV) exhibiting contrasting virulence in rainbow trout

“…As the presenting protein, to facilitate viropexis membrane fusion of the G-protein, viruses are required to reconfigure from a non-fusogenic to a fusogenic state, reviewed by Da Poian et al [46]. Using a model devised by Walker & Kongsuwan [47], Rocha et al [48] proposed hypothetical fusion peptides are positioned between residues 142 and 159.…”

Receptors and routes of dengue virus entry into the host cells

“…Viral fusion proteins are grouped in three major classes based on structural differences (Da Poian, Carneiro and Stauffer 2005;Harrison 2008;Modis 2014). Flaviviruses and alphaviruses bear class II fusion proteins, which are β-sheet-rich proteins that form homodimers at neutral pH, with the hydrophobic fusion loop located at the distal end of DII, buried in the dimer interface (Pierson and Kielian 2013).…”