Interaction with Tsg101 Is Necessary for the Efficient Transport and Release of Nucleocapsids in Marburg Virus-Infected Cells

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Marburg virus (MARV) is endemic in central Africa and causes hemorrhagic fever in humans and non-human primates, with high lethality. Presumably, the disease severity primarily depends on the response of host-cell factors interacting with viral proteins. We generated a recombinant MARV encoding an NP with a mutated PSAP late domain motif, which has previously been shown to mediate interaction with the cellular ESCRT protein Tsg101. We found that the PSAP-mediated interaction with Tsg101 was important at several steps of MARV assembly before viral fission. First, the egress of mature rMARVPSAPmut nucleocapsids from viral inclusions was inhibited. Second, actin-driven transport of rMARVPSAPmut nucleocapsids was impaired, displaying significantly shortened trajectories and reduced movement in the cell periphery. Third, rMARVPSAPmut nucleocapsids accumulated in cell periphery, and the number of filopodia-associated nucleocapsids decreased, indicating that rMARVPSAPmut nucleocapsids were defective to enter filopodia, the major budding sites of MARV. These defects resulted in the attenuated growth of rMARVPSAPmut. Interestingly, IQGAP1, an actin cytoskeleton regulator which interacts with Tsg101, was also recruited to nucleocapsids in dependence of the PSAP late domain. Thus, the interaction of NP with Tsg101 not only impacts viral budding at the plasma membrane but also nucleocapsid transport through the cytoplasm.

Vyšlo v časopise: Interaction with Tsg101 Is Necessary for the Efficient Transport and Release of Nucleocapsids in Marburg Virus-Infected Cells. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004463
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004463

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