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

Journal Article · · Cell Reports
 [1];  [2];  [3];  [4];  [5];  [5];  [6];  [2];  [4];  [3];  [2];  [5]
  1. Icahn School of Medicine at Mount Sinai, New York, NY (United States); Washington Univ. School of Medicine, St. Louis, MO (United States)
  2. Washington Univ. School of Medicine, St. Louis, MO (United States)
  3. Univ. of Texas Medical Branch at Galveston, TX (United States)
  4. Univ. of California, Riverside, CA (United States)
  5. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
  6. Icahn School of Medicine at Mount Sinai, New York, NY (United States); J. Craig Venter Inst., Rockville, MD (United States)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH); Dept. of the Defense, Defense Threat Reduction Agency
Grant/Contract Number:
R01AI107056; U191099565; R01AI059536; U19AI109945; U19AI109664; HDTRA1-12-1-0051
OSTI ID:
1351395
Journal Information:
Cell Reports, Vol. 14, Issue 7; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 55 works
Citation information provided by
Web of Science

References (30)

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  • The Journal of Infectious Diseases, Vol. 196, Issue s2 https://doi.org/10.1086/520608
journal November 2007
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Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs journal January 2010
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Cited By (18)

Characterization of a filovirus (Měnglà virus) from Rousettus bats in China journal January 2019
Relevance of Ebola virus VP35 homo-dimerization on the type I interferon cascade inhibition journal January 2019
Filovirus Strategies to Escape Antiviral Responses book January 2017
Post-exposure treatments for Ebola and Marburg virus infections journal January 2018
Intracellular sensing of viral genomes and viral evasion journal December 2019
A comparison of host gene expression signatures associated with infection in vitro by the Makona and Ecran (Mayinga) variants of Ebola virus journal February 2017
A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever journal December 2016
Recent advances in marburgvirus research journal January 2019
Role of Type I Interferons on Filovirus Pathogenesis journal February 2019
Expression of microRNA in human retinal pigment epithelial cells following infection with Zaire ebolavirus journal October 2019
Erratum: Post-exposure treatments for Ebola and Marburg virus infections journal May 2018
Comparison of Transcriptomic Platforms for Analysis of Whole Blood from Ebola-Infected Cynomolgus Macaques journal November 2017
Immune correlates of postexposure vaccine protection against Marburg virus journal February 2020
Retinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye journal July 2017
Quantification of Ebola virus replication kinetics in vitro journal November 2020
Egyptian Rousette IFN-ω Subtypes Elicit Distinct Antiviral Effects and Transcriptional Responses in Conspecific Cells journal March 2020
Marburg Virus Reverse Genetics Systems journal June 2016
Host Transcriptional Response to Ebola Virus Infection journal September 2017

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Related Subjects

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