Lipid Membranes Facilitate Conformational Changes Required for Reovirus Cell Entry

Area of Science:

• Virology
• Structural Biology
• Cellular Biology

Background:

• Viral entry into host cells requires significant conformational changes in viral proteins.
• These changes are typically triggered by environmental cues like low pH or interactions with host cell receptors and proteins.
• The specific trigger for infectious subviral particle (ISVP)-to-ISVP* conversion in reoviruses, crucial for genome delivery, remained unidentified.

Purpose of the Study:

• To investigate the physiological trigger for ISVP-to-ISVP* conversion during reovirus cell entry.
• To determine if interactions with lipid membranes can induce the necessary conformational changes for nonenveloped virus entry.
• To elucidate a novel mechanism of viral cell entry mediated by membrane interactions.

Main Methods:

• Utilized structural studies to predict the role of reovirus protein μ1 interactions with lipid head groups.
• Experimentally tested the effect of polyanions (sulfate, phosphate) and liposomes on ISVP-to-ISVP* conversion.
• Assessed the influence of various charged and uncharged lipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, sulfatide) on ISVP* formation.

Main Results:

• Polyanions and liposomes were found to facilitate the ISVP-to-ISVP* conversion.
• Specific charged lipids, phosphatidylcholine and phosphatidylethanolamine, promoted ISVP* formation.
• Other lipids, like sphingomyelin and sulfatide, did not promote or even inhibited ISVP* formation, indicating selectivity in membrane interaction.

Conclusions:

• Interactions with lipid membranes can serve as a trigger for nonenveloped virus entry.
• This study provides the first experimental evidence for membrane-initiated conformational changes in reovirus entry.
• Identified a novel cell entry strategy for nonenveloped viruses utilizing lipid membrane interactions.