@article{c4d0fcab4a974d17930ec0b52886020b,
title = "Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes",
abstract = "Non-retroviral integrated RNA viral sequences (NIRVs) potentially encoding ∼280 amino acid homologs to filovirus VP35 proteins are present across the Myotis genus of bats. These are estimated to have been maintained for ∼18 million years, indicating their co-option. To address the reasons for co-option, 16 Myotis VP35s were characterized in comparison to VP35s from the extant filoviruses Ebola virus and Marburg virus, in which VP35s play critical roles in immune evasion and RNA synthesis. The Myotis VP35s demonstrated a conserved suppression of innate immune signaling, albeit with reduced potency, in either human or Myotis cells. Their attenuation reflects a lack of dsRNA binding that in the filoviral VP35s correlates with potent suppression of interferon responses. Despite divergent function, evolution has preserved in Myotis the structure of the filoviral VP35s, indicating that this structure is critical for co-opted function, possibly as a regulator of innate immune signaling.",
keywords = "Ebola virus, Marburg virus, Myotis bats, VP35, evolution, filovirus, non-retroviral integrated RNA viral sequence",
author = "Edwards, {Megan R.} and Hejun Liu and Shabman, {Reed S.} and Ginell, {Garrett M.} and Priya Luthra and Parmeshwaran Ramanan and Keefe, {Lisa J.} and Bernd K{\"o}llner and Amarasinghe, {Gaya K.} and Taylor, {Derek J.} and Leung, {Daisy W.} and Basler, {Christopher F.}",
note = "Funding Information: This work was supported by NIH grant AI109945 (to C.F.B., G.K.A., and D.W.L.) and by Department of the Defense, Defense Threat Reduction Agency grants HDTRA1-17-1-0005 and HDTRA1-16-1-0033 (to C.F.B. and G.K.A.). C.F.B. is a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis. This research used resources at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline 17-ID, supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute . This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under contract DE-AC02-06CH11357 . We also thank the staff at SBC/Sector 19 at the Argonne National Laboratory for beamline access. 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 Alesha Grant and Gayathri Vijayakumar for assistance with preliminary studies and Sampriti De for technical support. Funding Information: This work was supported by NIH grant AI109945 (to C.F.B., G.K.A., and D.W.L.) and by Department of the Defense, Defense Threat Reduction Agency grants HDTRA1-17-1-0005 and HDTRA1-16-1-0033 (to C.F.B. and G.K.A.). C.F.B. is a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis. This research used resources at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline 17-ID, supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under contract DE-AC02-06CH11357. We also thank the staff at SBC/Sector 19 at the Argonne National Laboratory for beamline access. 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 Alesha Grant and Gayathri Vijayakumar for assistance with preliminary studies and Sampriti De for technical support. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = jul,
day = "24",
doi = "10.1016/j.celrep.2018.06.045",
language = "English",
volume = "24",
pages = "861--872.e6",
journal = "Cell Reports",
issn = "2211-1247",
number = "4",
}