Marburg virus exploits the Rab11-mediated endocytic pathway in viral-particle production

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Filoviruses, like Marburg virus (MARV), form filamentous particles.
• The viral matrix protein VP40 is crucial for particle formation and egress.
• The role of the Rab11 endocytic pathway in MARV particle production was unclear.

Purpose of the Study:

• To investigate the involvement of the small GTPase Rab11-mediated endocytic pathway in MARV particle formation and budding.
• To elucidate the molecular mechanisms by which VP40 facilitates viral egress.

Main Methods:

• Assessed Rab11 localization in cells expressing MARV VP40.
• Incorporated Rab11 into MARV-like particles and analyzed VP40 distribution.
• Used dominant-negative Rab11 and Rab11 knockdown to study viral release.
• Investigated the interaction between VP40, microtubules (α-tubulin), and Rab11.

Main Results:

• Rab11 localized diffusely in VP40-expressing cells and was incorporated into MARV-like particles.
• Rab11 downregulation reduced VP40 at the cell periphery and MARV particle release.
• VP40 induced microtubule redistribution to the cell periphery, which was partly Rab11-dependent.
• VP40 physically interacted with α-tubulin, not Rab11, and microtubule depolymerization impaired VP40 accumulation and particle formation.

Conclusions:

• Marburg virus VP40 utilizes microtubules to drive Rab11-positive vesicle trafficking to the cell surface for particle formation and egress.
• Filoviruses, in general, appear to hijack microtubule-dependent vesicle-trafficking machinery for replication.
• This pathway represents a potential target for broad-spectrum filovirus therapeutics.