Electron tomography reveals the steps in filovirus budding

Area of Science:

• Virology
• Cell Biology
• Structural Biology

Background:

• Filoviruses (Marburg, Ebola) cause severe hemorrhagic fever with high mortality.
• The mechanism of filovirus particle release from host cells remains poorly understood.
• Contrasting models, 'submarine-like' and 'rocket-like' budding, have been proposed.

Purpose of the Study:

• To elucidate the three-dimensional sequence of events during Marburg virus budding and release.
• To reconcile conflicting models of filovirus morphogenesis.
• To identify cellular factors influencing filovirus particle shape and infectivity.

Main Methods:

• Infection of cells with Marburg virus under Biosafety Level 4 (BSL-4) containment.
• Three-dimensional reconstruction using electron tomography of plastic-embedded cells.
• Analysis of virus-cell interactions during budding and release.

Main Results:

• Highly infectious filamentous Marburg virus particles are released early in infection.
• Budding involves lateral nucleocapsid association with the plasma membrane, followed by end-initiated envelopment.
• Scission occurs at the rear of the virus, causing local membrane instability.
• Prolonged infection leads to plasma membrane vesiculation, altering virus shape and infectivity.

Conclusions:

• The study details a novel, unified mechanism for Marburg virus budding and release.
• This mechanism reconciles previous 'submarine' and 'rocket' budding models.
• Cellular processes influence filovirus shape and infectivity, suggesting a general model for filamentous virus release.