Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Marburg virus (MARV) and ebolaviruses are filoviruses causing severe hemorrhagic fever.
• Viral entry involves fusion of host and viral membranes, facilitated by the GP2 fusion subunit.
• The GP2 N-terminal fusion loop (FL) is crucial for membrane disruption during fusion.

Purpose of the Study:

• To investigate the structure and function of the MARV GP2 FL.
• To elucidate the mechanism of MARV GP2-mediated cell entry.

Main Methods:

• Circular dichroism and nuclear magnetic resonance spectroscopy to monitor conformational changes.
• Liposome leakage assays to assess membrane disruption.
• Lipid bicelle NMR and mutational analysis to compare MARV and Ebola virus GP2 FL.

Main Results:

• The MARV GP2 FL exhibits pH-dependent conformational changes.
• At low pH, the MARV GP2 FL induces content leakage from liposomes, indicating membrane disruption.
• Structural differences were identified between MARV and Ebola virus GP2 FL.

Conclusions:

• The MARV GP2 FL plays a key role in membrane fusion through pH-dependent structural changes and lipid perturbation.
• Understanding these differences provides novel insights into MARV cell entry mechanisms.