Metal-induced conformational changes in the Sabiá virus spike complex

Area of Science:

• Structural biology
• Virology
• Molecular mechanisms

Background:

• Arenaviridae viruses, including hemorrhagic fever viruses, pose significant public health risks due to their potential for lethal outbreaks and limited therapeutic options.
• Structural data for 'Old World' arenavirus spike proteins exist, but a lack of corresponding structures for 'New World' arenaviruses, like Sabiá virus, hinders comparative analysis of viral entry mechanisms.

Purpose of the Study:

• To determine the structure of the Sabiá virus spike complex, responsible for mediating viral attachment and host cell entry.
• To elucidate the conformational states of the Sabiá virus spike protein and identify factors influencing its activation during cell entry.

Main Methods:

• Single-particle cryo-electron microscopy (cryo-EM) was employed to resolve the structure of the isolated Sabiá virus spike complex.
• High-resolution structural analysis was performed on two distinct conformational states of the spike protein.

Main Results:

• The study presents the cryo-EM structure of the Sabiá virus spike complex in both its native closed state (2.6 Å resolution) and an open state (2.9 Å resolution) adopted during cell entry.
• The conformational transition of the spike protein to its open state and subsequent cell entry were found to be dependent on acidic pH and an unidentified metal ion.

Conclusions:

• The determined structures provide critical insights into the molecular architecture of a 'New World' arenavirus spike protein.
• Findings suggest potential divergence in cell entry mechanisms between clade B arenaviruses and other members of the Arenaviridae family, highlighting the need for further investigation into arenavirus diversity.