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Cell Rep. 2016 Feb 23;14(7):1632-1640. doi: 10.1016/j.celrep.2016.01.049. Epub 2016 Feb 11.

Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins.

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
4
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
5
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Virology Group, J. Craig Venter Institute, Rockville, MD 20850, USA.
7
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: gamarasinghe@path.wustl.edu.
8
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: chris.basler@mssm.edu.

Abstract

Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitory domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our studies reveal functional differences in EBOV versus MARV VP35 RNA binding that result in unexpected differences in the host response to deadly viral pathogens.

KEYWORDS:

RIG-I like receptor; VP35; filovirus; immune evasion; pattern associated molecular pattern (PAMP); type I interferon

PMID:
26876165
PMCID:
PMC4767585
DOI:
10.1016/j.celrep.2016.01.049
[Indexed for MEDLINE]
Free PMC Article

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