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Published on: March 1, 2019
Molecular and cellular aspects of rhabdovirus entry
Aurélie A V Albertini1, Eduard Baquero, Anna Ferlin
1Laboratoire de Virologie Moléculaire et Structurale, Centre de Recherche de Gif, CNRS (UPR 3296), Avenue de la Terrasse, 91198, Gif sur Yvette Cedex, France. alberti@vms.cnrs-gif.fr
Abstract:
Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell.
Insights
Rhabdoviruses use a unique viral glycoprotein (G) for cell entry and membrane fusion. Structural analysis reveals G combines features of known fusion classes, offering new insights into viral infection mechanisms.
Area of Science:
- Virology
- Structural Biology
- Cell Biology
Background:
- Rhabdoviruses infect cells through endocytosis, requiring membrane fusion within acidic endosomes.
- Viral glycoprotein G mediates both receptor binding and low-pH triggered membrane fusion.
Purpose of the Study:
- To present the atomic structures of vesicular stomatitis virus (VSV) G in its pre- and post-fusion conformations.
- To compare VSV G structure with known viral fusion proteins (class I and II).
- To provide an integrated view of rhabdovirus entry pathways.
Main Methods:
- Elucidation of atomic structures of VSV G in pre- and post-fusion states.
- Comparative analysis of VSV G structures with established viral fusion protein classes.
- Integration of structural data with recent findings on cellular aspects of rhabdovirus infection.
Main Results:
- VSV G exhibits a pH-dependent equilibrium between pre- and post-fusion conformations.
- VSV G structure shares features with both class I and class II viral fusion proteins.
- Unique structural particularities of VSV G expand understanding of viral fusion machineries.
Conclusions:
- VSV G is an atypical fusion protein, distinct from previously characterized classes.
- Understanding VSV G structure provides novel insights into viral membrane fusion mechanisms.
- Integrated data offer a comprehensive view of rhabdovirus host cell entry.
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