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

Megan R. Edwards, Gai Liu, Chad E. Mire, Suhas Sureshchandra, Priya Luthra, Benjamin Yen, Reed S. Shabman, Daisy W. Leung, Ilhem Messaoudi, Thomas W. Geisbert, Gaya K. Amarasinghe, Christopher F. Basler

Research output: Contribution to journalArticle

38 Scopus citations

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. Edwards et al. demonstrate that although the VP35 proteins of both Ebola and Marburg viruses function to suppress RIG-I signaling and block interferon α/β production, Ebola virus is a more potent inhibitor of the response. This is due, in part, to more efficient RNA recognition by Ebola virus VP35.

Original languageEnglish (US)
Pages (from-to)1632-1640
Number of pages9
JournalCell Reports
Volume14
Issue number7
DOIs
StatePublished - Feb 23 2016

Keywords

  • Filovirus
  • Immune evasion
  • Pattern associated molecular pattern (PAMP)
  • RIG-I like receptor
  • Type I interferon
  • VP35

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Edwards, M. R., Liu, G., Mire, C. E., Sureshchandra, S., Luthra, P., Yen, B., Shabman, R. S., Leung, D. W., Messaoudi, I., Geisbert, T. W., Amarasinghe, G. K., & Basler, C. F. (2016). Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins. Cell Reports, 14(7), 1632-1640. https://doi.org/10.1016/j.celrep.2016.01.049