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.
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.