Peptides released from reovirus outer capsid form membrane pores that recruit virus particles

Area of Science:

• Virology
• Cell Biology
• Biophysics

Background:

• Nonenveloped viruses require cell membrane disruption for entry.
• Reovirus entry involves capsid protein mu1 and red blood cell (RBC) membrane pore formation.

Purpose of the Study:

• To investigate the role of reovirus capsid protein mu1 fragments in cell membrane pore formation.
• To determine if released mu1 fragments are sufficient for pore formation and virus attachment.

Main Methods:

• Analysis of reovirus structural changes and protein fragment release.
• Incubation of RBCs with reovirus particles, mu1 fragments, and mutant forms.
• Assessing pore formation and membrane association using biophysical techniques.

Main Results:

• Myristoylated N-terminal fragment (mu1N) and C-terminal fragment (phi) are released from reovirus particles.
• Both mu1N and phi associate with RBC membranes and form pores independently.
• mu1N plays the primary role in pore formation; mutant reovirus lacking mu1N release cannot form pores or attach to membranes.
• Preformed pores, created by wild-type peptides or synthetic mu1N, can recruit mutant reovirus particles.

Conclusions:

• Released reovirus mu1 fragments, especially mu1N, are sufficient for creating size-selective pores in RBC membranes.
• Pore formation by released peptides precedes and facilitates virus particle docking to the membrane.
• This mechanism highlights a critical step in viral cell entry and membrane penetration.