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

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

doi:10.1016/j.celrep.2016.01.049

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

Journal Article · Thu Feb 11 00:00:00 EST 2016 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2016.01.049· OSTI ID:1351395

Edwards, Megan R. ^[1]; Liu, Gai ^[2]; Mire, Chad E. ^[3]; Sureshchandra, Suhas ^[4]; Luthra, Priya ^[5]; Yen, Benjamin ^[5]; Shabman, Reed S. ^[6]; Leung, Daisy W. ^[2]; Messaoudi, Ilhem ^[4]; Geisbert, Thomas W. ^[3]; Amarasinghe, Gaya K. ^[2]; Basler, Christopher F. ^[5]

Icahn School of Medicine at Mount Sinai, New York, NY (United States); Washington Univ. School of Medicine, St. Louis, MO (United States)
Washington Univ. School of Medicine, St. Louis, MO (United States)
Univ. of Texas Medical Branch at Galveston, TX (United States)
Univ. of California, Riverside, CA (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States); J. Craig Venter Inst., Rockville, MD (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: Dept. of the Defense, Defense Threat Reduction Agency; NIH

OSTI ID:: 1351395

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 7 Vol. 14; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
RIG-I like receptor
VP35
filovirus
immune evasion
pattern associated molecular pattern (PAMP)
type I interferon

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

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References (40)

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