Postfusion structure of human-infecting Bourbon virus envelope glycoprotein

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Thogotoviruses are zoonotic viruses with significant public health implications.
• Bourbon virus (BRBV), a thogotovirus, has recently emerged in the US, causing human fatalities.
• Understanding viral fusion mechanisms is crucial for developing antiviral therapies.

Purpose of the Study:

• To determine the crystal structure of the Bourbon virus (BRBV) envelope glycoprotein.
• To elucidate the postfusion conformation of the BRBV glycoprotein.
• To compare the structural features of BRBV glycoprotein with other viral fusion proteins.

Main Methods:

• X-ray crystallography was employed to determine the three-dimensional structure of the BRBV envelope glycoprotein.
• Bioinformatic analyses were performed to compare the structure with homologous viral proteins.

Main Results:

• The crystal structure of the BRBV envelope glycoprotein in its postfusion conformation was determined.
• The glycoprotein exhibits a typical class III viral fusion protein fold.
• An extensive positively charged electrostatic potential was observed, similar to Dhori virus glycoprotein.
• Thogotovirus glycoproteins share greater structural similarity with herpes virus glycoprotein Bs than with rhabdovirus G proteins.

Conclusions:

• The determined structure provides insights into the fusion mechanism of BRBV.
• Class III viral fusion proteins display significant structural diversity, suggesting the evolution of distinct subclasses.
• This research contributes to understanding thogotovirus evolution and informs potential therapeutic interventions.