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Structure and characterization of Crimean-Congo hemorrhagic fever virus GP38

DOI: 10.1128/JVI.02005-19 DOI Help

Authors: Akaash K. Mishra (University of Texas at Austin) , Crystal L. Moyer (Mapp Biopharmaceutical) , Dafna M. Abelson (Mapp Biopharmaceutical) , Daniel J. Deer (University of Texas Medical Branch) , Kamel El Omari (University of Oxford) , Ramona Duman (Diamond Light Source) , Leslie Lobel (Ben-Gurion University of the Negev) , Julius J. Lutwama (Emerging and Re-Emerging Infection Uganda Virus Research Institute) , John M. Dye (US Army Medical Research Institute of Infectious Diseases) , Armin Wagner (Diamond Light Source) , Kartik Chandran (Albert Einstein College of Medicine) , Robert W. Cross (University of Texas Medical Branch) , Thomas W. Geisbert (University of Texas Medical Branch) , Larry Zeitlin (Mapp Biopharmaceutical) , Zachary A. Bornholdt (Mapp Biopharmaceutical) , Jason S. Mclellan (University of Texas at Austin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: January 2020

Open Access Open Access

Abstract: Crimean–Congo hemorrhagic fever virus (CCHFV) is the causative agent of the most widespread tick-borne viral infection in humans. CCHFV encodes a secreted glycoprotein (GP38) of unknown function that is the target of a protective antibody. Here we present the crystal structure of GP38 at a resolution of 2.5 Å, which revealed a novel fold primarily consisting of a 3-helix bundle and a β-sandwich. Sequence alignment and homology modeling showed distant homology between GP38 and the ectodomain of Gn (a structural glycoprotein in CCHFV), suggestive of a gene duplication event. Analysis of convalescent sera showed high titers of GP38 antibodies indicating immunogenicity in humans during natural CCHFV infection. The only protective antibody for CCHFV in an adult mouse model reported to date, 13G8, bound GP38 with sub-nanomolar affinity and protected against heterologous CCHFV challenge in a STAT1-knockout mouse model. Our data strongly suggests that GP38 should be evaluated as a vaccine antigen and its structure provides a foundation to investigate functions of this protein in the viral life cycle.

Diamond Keywords: Crimean-Congo Hemorrhagic Fever (CCHF); Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I23-Long wavelength MX

Documents:
JVI.02005-19.full.pdf

Discipline Tags:

Biophysics Disease in the Developing World Drug Discovery Health & Wellbeing Infectious Diseases Life Sciences & Biotech Pathogens Structural biology Vaccines

Technical Tags:

Diffraction Long Wavelength Crystallography Macromolecular Crystallography (MX)