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Vertebrate-class-specific binding modes of the alphavirus receptor MXRA8.
Zimmerman, Ofer; Zimmerman, Maxwell I; Raju, Saravanan; Nelson, Christopher A; Errico, John M; Madden, Emily A; Holmes, Autumn C; Hassan, Ahmed O; VanBlargan, Laura A; Kim, Arthur S; Adams, Lucas J; Basore, Katherine; Whitener, Bradley M; Palakurty, Sathvik; Davis-Adams, Hannah G; Sun, Chengqun; Gilliland, Theron; Earnest, James T; Ma, Hongming; Ebel, Gregory D; Zmasek, Christian; Scheuermann, Richard H; Klimstra, William B; Fremont, Daved H; Diamond, Michael S.
Afiliação
  • Zimmerman O; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Zimmerman MI; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Raju S; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Nelson CA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Errico JM; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Madden EA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Holmes AC; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Hassan AO; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • VanBlargan LA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Kim AS; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Adams LJ; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Basore K; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Whitener BM; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Palakurty S; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Davis-Adams HG; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Sun C; Center for Vaccine Research, Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Gilliland T; Center for Vaccine Research, Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Earnest JT; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Ma H; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • Ebel GD; Center for Vector-borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
  • Zmasek C; J. Craig Venter Research Institute, La Jolla, CA 92037, USA.
  • Scheuermann RH; J. Craig Venter Research Institute, La Jolla, CA 92037, USA; Department of Pathology, University of California, San Diego, San Diego, CA 92161, USA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA; Global Virus Network, Baltimore, MD 92037, USA.
  • Klimstra WB; Center for Vaccine Research, Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Fremont DH; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University Schoo
  • Diamond MS; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, M
Cell ; 186(22): 4818-4833.e25, 2023 10 26.
Article em En | MEDLINE | ID: mdl-37804831
ABSTRACT
MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian reservoirs. Here, we show that avian, but not mammalian, MXRA8 can act as a receptor for Sindbis, western equine encephalitis (WEEV), and related alphaviruses with avian reservoirs. Structural analysis of duck MXRA8 complexed with WEEV reveals an inverted binding mode compared with mammalian MXRA8 bound to CHIKV. Whereas both domains of mammalian MXRA8 bind CHIKV E1 and E2, only domain 1 of avian MXRA8 engages WEEV E1, and no appreciable contacts are made with WEEV E2. Using these results, we generated a chimeric avian-mammalian MXRA8 decoy-receptor that neutralizes infection of multiple alphaviruses from distinct antigenic groups in vitro and in vivo. Thus, different alphaviruses can bind MXRA8 encoded by different vertebrate classes with distinct engagement modes, which enables development of broad-spectrum inhibitors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Alphavirus Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Alphavirus Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article