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


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.

SUBMITTER: Halldorsson S 

PROVIDER: S-EPMC4932967 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Halldorsson Steinar S   Behrens Anna-Janina AJ   Harlos Karl K   Huiskonen Juha T JT   Elliott Richard M RM   Crispin Max M   Brennan Benjamin B   Bowden Thomas A TA  

Proceedings of the National Academy of Sciences of the United States of America 20160620 26


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  ...[more]

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