Journal
CELL REPORTS
Volume 14, Issue 7, Pages 1632-1640Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.01.049
Keywords
-
Categories
Funding
- NIH [R01AI107056, U191099565, R01AI059536, U19AI109945, U19AI109664]
- Department of the Defense, Defense Threat Reduction Agency [HDTRA1-12-1-0051]
Ask authors/readers for more resources
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-alpha/beta (IFN-alpha/beta) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available