Abstract
AbstractFollowing endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K+] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical bunyavirus. Here, we use sub-tomogram averaging and AlphaFold, to generate a pseudo-atomic model of the whole BUNV glycoprotein envelope. We unambiguously locate the Gc fusion domain and its chaperone Gn within the floor domain of the spike. Furthermore, viral incubation at low pH and high [K+], reminiscent of endocytic conditions, results in a dramatic rearrangement of the BUNV envelope. Structural and biochemical assays indicate that pH 6.3/K+ in the absence of a target membrane elicits a fusion-capable triggered intermediate state of BUNV GPs; but the same conditions induce fusion when target membranes are present. Taken together, we provide mechanistic understanding of the requirements for bunyavirus entry.
Funder
Academy of Medical Sciences
Human Frontier Science Program
RCUK | MRC | Medical Research Foundation
Wellcome Trust
RCUK | Biotechnology and Biological Sciences Research Council
University of Leeds
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference53 articles.
1. Briese, T., Calisher, C. H. & Higgs, S. Viruses of the family Bunyaviridae: are all available isolates reassortants? Virology 446, 207–216 (2013).
2. Elliott, R. M. Emerging viruses: the Bunyaviridae. Mol. Med. 3, 572–577 (1997).
3. Abudurexiti, A. et al. Taxonomy of the order Bunyavirales: update 2019. Arch Virol. 164, 1–17 (2019).
4. Elliott, R. M. Orthobunyaviruses: Recent genetic and structural insights. Nat. Rev. Microbiol. 12, 673–685 (2014).
5. Bowden, T. A. et al. Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike. PLOS Pathog. 9, e1003374 (2013).