Abstract
Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here we investigated how endosomal F trafficking affects HeV assembly. We found that the HeV matrix (M) and F proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-only or F-only VLPs. Mutations to the F protein transmembrane domain or cytoplasmic tail that disrupted endocytic trafficking led to failure of F to function with M for VLP assembly. Wild-type F functioned normally for VLP assembly even when its cleavage was prevented with a cathepsin inhibitor, indicating that it is endocytic F trafficking that is important for VLP assembly, not proteolytic F cleavage. Under specific conditions of reduced M expression, we found that M could no longer induce significant VLP release but retained the ability to be incorporated as a passenger into F-driven VLPs, provided that the F protein was competent for endocytic trafficking. The F and M proteins were both found to traffic through Rab11-positive recycling endosomes (REs), suggesting a model in which F and M trafficking pathways converge at REs, enabling these proteins to preassemble before arriving at plasma membrane budding sites.
Document Type
Article
Publication Date
7-2017
Digital Object Identifier (DOI)
https://doi.org/10.1128/JVI.00152-17
Funding Information
This work was supported in part by NIH grants AI108260 to A.P.S. and R.E.D., AI057168 to A.P.S., and RR020171 to R.E.D., as well as USDA grant PEN04497 to A.P.S.
Repository Citation
Cifuentes-Muñoz, Nicolás P.; Sun, Weina; Ray, Greeshma; Schmitt, Phuong Tieu; Webb, Stacy; Gibson, Kathleen; Dutch, Rebecca Ellis; and Schmitt, Anthony P., "Mutations in the Transmembrane Domain and Cytoplasmic Tail of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly" (2017). Molecular and Cellular Biochemistry Faculty Publications. 116.
https://uknowledge.uky.edu/biochem_facpub/116
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Immunology and Infectious Disease Commons, Virology Commons
Notes/Citation Information
Published in Journal of Virology, v. 91, issue 14, e00152-17, p. 1-16.
Copyright © 2017 American Society for Microbiology. All Rights Reserved.
The copyright holder has granted the permission for posting the article here.