@article{6b5643b6dade4e7f8eab5a95f82af6f5,
title = "Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins",
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.",
keywords = "Filovirus, Immune evasion, Pattern associated molecular pattern (PAMP), RIG-I like receptor, Type I interferon, VP35",
author = "Edwards, {Megan R.} and Gai Liu and Mire, {Chad E.} and Suhas Sureshchandra and Priya Luthra and Benjamin Yen and Shabman, {Reed S.} and Leung, {Daisy W.} and Ilhem Messaoudi and Geisbert, {Thomas W.} and Amarasinghe, {Gaya K.} and Basler, {Christopher F.}",
note = "Funding Information: This work is supported in part by NIH grants (R01AI107056 to D.W.L.; U191099565 to G.K.A.; R01AI059536 to C.F.B.; U19AI109945 [Basler-PI] to C.F.B., G.K.A., I.M., and T.W.G.; and U19AI109664 [Basler-PI] to C.F.B. and G.K.A.) and by Department of the Defense, Defense Threat Reduction Agency grant HDTRA1-12-1-0051 (to C.F.B., G.K.A., and T.W.G.). The content of the information does not necessarily reflect the position or the policy of the federal government and no official endorsement should be inferred. We thank Christine Schwall-Pecci for help with manuscript editing. Funding Information: This work is supported in part by NIH grants (R01AI107056 to D.W.L.; U191099565 to G.K.A.; R01AI059536 to C.F.B.; U19AI109945 [Basler-PI] to C.F.B., G.K.A., I.M., and T.W.G.; and U19AI109664 [Basler-PI] to C.F.B. and G.K.A.) and by Department of the Defense, Defense Threat Reduction Agency grant HDTRA1-12-1-0051 (to C.F.B., G.K.A., and T.W.G.). The content of the information does not necessarily reflect the position or the policy of the federal government and no official endorsement should be inferred. We thank Christine Schwall-Pecci for help with manuscript editing. Publisher Copyright: {\textcopyright} 2016 The Authors.",
year = "2016",
month = feb,
day = "23",
doi = "10.1016/j.celrep.2016.01.049",
language = "English (US)",
volume = "14",
pages = "1632--1640",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}