131 Replication and assembly of filoviruses

The family of Filoviridae comprises Marburg and Ebola virus which both cause severe life-threatening diseases characterized by high fever, rash, thrombocytopenia and hemorrhagic diathesis. The pathogenesis of the syndrome is not completely understood; probably the dynamic replication of filoviruses in the infected host leads to an uncoordinated immune response. Detailed understanding of the basic mechanisms of filoviral assembly and interaction with host cells is key to identify targets of antiviral intervention. The first sign of filovirus replication that can be detected microscopically in the infected cell is the formation of inclusions in the perinuclear region. Inclusions contain all filoviral nucleocapsid proteins (NP, VP35, VP30, VP24, and L) but also the matrix protein VP40 and a number of cellular proteins. Viral nucleocapsids are formed within the inclusions by specific interactions among the viral proteins. Mature nucleocapsids are transported across the cytoplasm to the plasma membrane with the help of the actin cytoskeleton. In the cell periphery nucleocapsids are associated with the matrix protein and channeled into filopodia, the site of filoviral release. Nucleocapsids inside filopodia are cotransported together with the unconventional motor protein myosin 10. Transport of nucleocapsids and release of viral particles is supported by the cellular ESCRT machinery.