TY - JOUR T1 - Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus A1 - Valmas, Charalampos A1 - Grosch, Melanie N. A1 - Schümann, Michael A1 - Olejnik, Judith A1 - Martinez, Osvaldo A1 - Best, Sonja M. A1 - Krähling, Verena A1 - Basler, Christopher F. A1 - Mühlberger, Elke Y1 - 2010/01/15 N2 - Author Summary The closely related members of the filovirus family, Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic disease in humans with high fatality rates. Infected individuals exhibit dysregulated immune responses which appear to result from several factors, including virus-mediated impairment of innate immune responses. Previous studies demonstrated that both MARV and EBOV block the type I interferon-induced Jak-STAT signaling pathway. For EBOV, the viral protein VP24 mediates the inhibitory effects by interfering with the nuclear translocation of activated STAT proteins. Here, we show that MARV uses a distinct mechanism to block IFN signaling pathways. Our data revealed that MARV blocks the phosphorylation of Janus kinases and their target STAT proteins in response to type I and type II interferon and interleukin 6. Surprisingly, the observed inhibition is not achieved by the MARV VP24 protein, but by the matrix protein VP40 which also mediates viral budding. Over-expression studies indicate that MARV VP40 globally antagonizes Jak1-dependent signaling. Further, we show that a MARV VP40 mutant defective for budding retains interferon antagonist function. Our results highlight a basic difference between EBOV and MARV, define a new function for MARV VP40 and reveal new targets for the development of anti-MARV therapies. JF - PLOS Pathogens JA - PLOS Pathogens VL - 6 IS - 1 UR - https://doi.org/10.1371/journal.ppat.1000721 SP - e1000721 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1000721 ER -