Forty-Five Years of Marburg Virus Research

Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith

When MARV was adapted to non-or less permissive animals, such as mouse and guinea pig, the adapted viruses showed mutations in VP40. Two of the amino acid changes in the mouse-adapted MARV VP40 have been shown to be essential for the inhibition of IFN signaling in mouse cells, underlining the importance of IFN suppression for the virulence and host specificity of MARV [125, 130, 131] . The protein product of the sixth gene, VP24, is unique to the filovirus family. VP24 is generally addressed as a second, minor matrix protein. However, cryo-electron tomography analysis of viral particles showed that VP24 is located in close proximity to the nucleocapsid proteins, suggesting that it might be part of the nucleocapsid complex [60] . VP24 can easily be released from virion-associated nucleocapsids by treatment with increasing salt concentrations, indicating that it is only loosely connected to the nucleocapsid [115] . Intracellular localization studies of VP24 showed that a minor part of the protein (approx. 10%) is weakly bound to cellular membranes, including filopodia enriched with VP40. VP24 is also distributed diffusely in the cytoplasm, relocalizes to nucleocapsid-containing inclusions, and is found in association with free nucleocapsids. Co-expression of NP and VP24 is sufficient to direct VP24 to NP inclusions in the cytoplasm [132] . Functional studies on MARV VP24 suggest that the protein is important for the release of viral particles in the context of infection, although it influences neither the morphology of VP40-derived VLPs nor the efficiency of VLP release. In addition, RNAi-mediated knockdown of VP24 in MARV-infected cells had no impact on viral genome replication, indicating that VP24 is involved in a step after replication and before budding [132] . According to the model that has been proposed based on these data, VP24 is involved in the maturation of transport-competent nucleocapsids and/or mediates the interaction between nucleocapsids and budding sites at the plasma membrane [132] . There is also evidence that MARV VP24 affects transcription and replication in a transcription and replication competent VLP system [113] .