Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion.

TitleStructure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion.
Publication TypeJournal Article
Year of Publication2016
AuthorsHalldorsson S, Behrens A-J, Harlos K, Huiskonen JT, Elliott RM, Crispin M, Brennan B, Bowden TA
JournalProc Natl Acad Sci U S A
Volume113
Issue26
Pagination7154-9
Date Published06/28/2016
ISSN1091-6490
Abstract

An emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (SFTSV) is responsible for thousands of clinical cases and associated fatalities in China, Japan, and South Korea. Akin to other phleboviruses, SFTSV relies on a viral glycoprotein, Gc, to catalyze the merger of endosomal host and viral membranes during cell entry. Here, we describe the postfusion structure of SFTSV Gc, revealing that the molecular transformations the phleboviral Gc undergoes upon host cell entry are conserved with otherwise unrelated alpha- and flaviviruses. By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever virus, we show that these changes involve refolding of the protein into a trimeric state. Reverse genetics and rescue of site-directed histidine mutants enabled localization of histidines likely to be important for triggering this pH-dependent process. These data provide structural and functional evidence that the mechanism of phlebovirus-host cell fusion is conserved among genetically and patho-physiologically distinct viral pathogens.

DOI10.1073/pnas.1603827113
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27325770
PubMed Central IDPMC4932967
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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