Abstract
Filoviruses such as Ebola and Marburg virus bud from the host membrane as enveloped virions. This process is achieved by the matrix protein VP40. When expressed alone, VP40 induces budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and generation of membrane curvature are intrinsic properties of VP40. There has been no direct information on the structure of VP40 matrix layers within viruses or virus-like particles. We present structures of Ebola and Marburg VP40 matrix layers in intact virus-like particles, and within intact Marburg viruses. VP40 dimers assemble extended chains via C-terminal domain interactions. These chains stack to form 2D matrix lattices below the membrane surface. These lattices form a patchwork assembly across the membrane and suggesting that assembly may begin at multiple points. Our observations define the structure and arrangement of the matrix protein layer that mediates formation of filovirus particles.
Highlights
The filovirus family includes viruses such as Ebola, Marburg, and Sudan viruses that can cause hemorrhagic fever and severe disease (Feldmann et al, 2013)
The structure of the matrix layer in EBOV virus-like particles (VLPs) Ebola virus VP40 (eVP40) expression induces budding of long VLPs from the surface of mammalian cells (Noda et al, 2002; Timmins et al, 2001)
We applied subtomogram averaging methods to determine the structure of the matrix layer to a resolution of 10 A (Figure 1, Figure 1—figure supplement 2) from intact eVP40 VLPs
Summary
The filovirus family includes viruses such as Ebola, Marburg, and Sudan viruses that can cause hemorrhagic fever and severe disease (Feldmann et al, 2013). VP40 is required for viral budding, and expression of VP40 alone is sufficient to drive formation of filamentous virus-like particles (VLPs) containing a matrix layer and membrane envelope (Harty et al, 2000; Jasenosky et al, 2001; Noda et al, 2002; Timmins et al, 2001). The morphology of these VLPs is similar to that of true virions but their diameter is smaller (Noda et al, 2002). When VP40 is co-expressed with NC components NP, VP24
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