@article{12b1d46aca5e4ba1bf101f9071436c65,
title = "An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis",
abstract = "Kim et al. identify a sequence insertion in the Mxra8 receptor of Bovinae species that prevents alphavirus binding. Deletion of the Bovinae Mxra8 insertion restores alphavirus infection, while mice engineered with the Mxra8 insertion exhibit reduced CHIKV infection. Identification of this insertion could facilitate countermeasures preventing Mxra8 engagement of alphaviruses.",
keywords = "Bovinae, X-ray crystallography, alphavirus, evolution, infection, pathogenesis, receptor",
author = "Kim, {Arthur S.} and Ofer Zimmerman and Fox, {Julie M.} and Nelson, {Christopher A.} and Katherine Basore and Rong Zhang and Lorellin Durnell and Chandni Desai and Christopher Bullock and Deem, {Sharon L.} and Jonas Oppenheimer and Beth Shapiro and Ting Wang and Sara Cherry and Coyne, {Carolyn B.} and Handley, {Scott A.} and Landis, {Michael J.} and Fremont, {Daved H.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by NIH grants R01AI114816 , R01AI123348 , R01AI095436 , and T32AI007172 and the Center for Structural Genomics of Infectious Diseases , contract number HHSN272201700060C. We thank Jay Nix at ALS beamline 4.2.2 for assistance with data collection and processing; James Womack and Terje Raudsepp for providing the primary Bovine fibroblasts and James Crowe for providing anti-alphavirus mAbs; Mary Duncan for arranging access to the non-domestic bovine tissues; the Genome Engineering and iPSC Center and Department of Pathology Microinjection Facility at Washington University for gRNA design and mouse generation; Larissa Thackray for design of the Mxra8 knockin mouse; and the Living Earth Collaborative, Jonathan Losos, Joseph Bielawski, and Terence Dermody for editorial suggestions. Funding Information: This study was supported by NIH grants R01AI114816, R01AI123348, R01AI095436, and T32AI007172 and the Center for Structural Genomics of Infectious Diseases, contract number HHSN272201700060C. We thank Jay Nix at ALS beamline 4.2.2 for assistance with data collection and processing; James Womack and Terje Raudsepp for providing the primary Bovine fibroblasts and James Crowe for providing anti-alphavirus mAbs; Mary Duncan for arranging access to the non-domestic bovine tissues; the Genome Engineering and iPSC Center and Department of Pathology Microinjection Facility at Washington University for gRNA design and mouse generation; Larissa Thackray for design of the Mxra8 knockin mouse; and the Living Earth Collaborative, Jonathan Losos, Joseph Bielawski, and Terence Dermody for editorial suggestions. A.S.K. O.Z. L.D. C.B.C. and S.C. performed the infection studies with Mxra8. O.Z. R.Z. and C.B. generated the Mxra8 genes and lentiviruses for the complementation studies. A.S.K. and K.B. performed the ELISA and BLI binding studies. A.S.K. C.A.N. K.B. and D.H.F. performed the structural analysis of mouse and cattle Mxra8 and the docking studies on CHIKV. S.L.D. provided key animal reagents. J.M.F. performed the in vivo studies. A.S.K. C.D. J.O. B.S. and S.A.H. analyzed the whole genome sequences and primary RNA sequences. T.W. provided the genetic analysis of the sequence insertion. M.J.L. and B.S. performed the evolutionary analysis. A.S.K. O.Z. J.M.F. and K.B. performed the data analysis. A.S.K. O.Z. M.J.L. and M.S.D. wrote the initial manuscript draft. M.S.D. is a consultant for Inbios and Emergent BioSolutions and is on the scientific advisory board of Moderna. D.H.F. is a founder of Courier Therapeutics. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = mar,
day = "11",
doi = "10.1016/j.chom.2020.01.008",
language = "English",
volume = "27",
pages = "428--440.e9",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "3",
}