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.

authors

Halldorsson S,Behrens AJ,Harlos K,Huiskonen JT,Elliott RM,Crispin M,Brennan B,Bowden TA

doi

10.1073/pnas.1603827113

subject

Has Abstract

pub_date

2016-06-28 00:00:00

pages

7154-9

issue

26

eissn

0027-8424

issn

1091-6490

pii

1603827113

journal_volume

113

pub_type

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