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Invasion and Replication Strategies of Pathogenes
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SP A13

Interaction of Marburg viral proteins VP40 and GP with cellular pathways


HD Dr. Stephan Becker
Institute of Virology, Philipps-University Marburg


Summary

Interaction of matrix protein, and envelope protein of Marburgvirus with cellular components. The nucleocapsid, the matrix proteins and the envelope protein of filoviruses are recruited to the plasma membrane or multivesicular bodies (MVBs) where budding of progeny takes place. The envelope protein is sorted exclusively to the apical cell pole upon single expression. In context of the filoviral infection, however, the envelope protein is also transported to the basolateral cell pole, where budding of virions can be observed. The key player in the assembly of progeny virions is represented by VP40, the major matrix protein of filoviruses. Soon after synthesis VP40 is attached to small lipid vesicles and is subsequently recruited to MVBs in the perinuclear region and later in peripheral MVB. Finally, VP40 is detected at the plasma membrane where it induces the formation of filamentous virus-like particles (VLP) which resemble closely the morphology of filoviruses. Matrix and envelope protein meet in MVBs which seem to represent the sites of formation of the viral envelope. Together with GP, specific lipid components are transported from the trans Golgi network to the MVBs.

The present project addresses the following questions: 1) VP40 is transported along the retrograde late endosomal route to the plasma membrane including several fusion and fission steps of transport vesicles. Factors that are essential for the assembly, fission and targeting of the vesicles should be identified to characterize the transport of VP40 in detail. 2) Intracellular transport of VP40 is dependent on the ytoskeleton. The influence of actin on the transport of VP40 will be investigated. 3) In the presence of VP40, the envelope protein undergoes redistribution from the classical secretory pathway to the endosomal compartment (MVBs). The effect of VP40 on the directed transport and distribution of the envelope protein
will be investigated in polarized cells.

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