دورية أكاديمية
Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus.
| العنوان: | Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus. |
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| المؤلفون: | Adams LJ; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Raju S; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Ma H; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Gilliland T Jr; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA., Reed DS; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA., Klimstra WB; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA., Fremont DH; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: fremont@wustl.edu., Diamond MS; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mdiamond@wustl.edu. |
| المصدر: | Cell [Cell] 2024 Jan 18; Vol. 187 (2), pp. 360-374.e19. Date of Electronic Publication: 2024 Jan 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | Cryoelectron Microscopy* , Encephalitis Virus, Eastern Equine*/physiology , Encephalitis Virus, Eastern Equine*/ultrastructure , Encephalomyelitis, Equine*/metabolism , Receptors, LDL*/ultrastructure, Animals ; Mice ; Alphavirus/physiology ; Horses ; Protein Binding |
| مستخلص: | The very-low-density lipoprotein receptor (VLDLR) comprises eight LDLR type A (LA) domains and supports entry of distantly related alphaviruses, including Eastern equine encephalitis virus (EEEV) and Semliki Forest virus (SFV). Here, by resolving multiple cryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesis and functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2 A domain) to engage more than one LA domain simultaneously. However, no single LA domain is necessary or sufficient to support efficient EEEV infection. Whereas all EEEV strains show conservation of two VLDLR-binding sites, the EEEV PE-6 strain and a few other EEE complex members feature a single amino acid substitution that enables binding of LA domains to an additional site on the E2 B domain. These structural and functional analyses informed the design of a minimal VLDLR decoy receptor that neutralizes EEEV infection and protects mice from lethal challenge. Competing Interests: Declaration of interests M.S.D. is a consultant or advisor for Inbios, Ocugen, Vir Biotechnology, Topspin Therapeutics, Moderna, Merck, and Immunome. The Diamond laboratory has received funding support from Emergent BioSolutions, Moderna, and Vir Biotechnology. D.H.F. is a founder of Courier Therapeutics and has received funding support from Emergent BioSolutions and Mallinckrodt Pharmaceuticals. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| التعليقات: | Update of: bioRxiv. 2023 Nov 15:2023.11.15.567188. doi: 10.1101/2023.11.15.567188. (PMID: 38014196) |
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| معلومات مُعتمدة: | R01 AI164653 United States AI NIAID NIH HHS; R01 AI095436 United States AI NIAID NIH HHS; R01 AI141436 United States AI NIAID NIH HHS; R01 AI153209 United States AI NIAID NIH HHS; R01 AI143673 United States AI NIAID NIH HHS; U19 AI142790 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: alphavirus; cryo-electron microscopy; encephalitis; mice; pathogenesis; receptor; therapeutic |
| المشرفين على المادة: | 0 (VLDL receptor) 0 (Receptors, LDL) |
| تواريخ الأحداث: | Date Created: 20240104 Date Completed: 20240129 Latest Revision: 20240610 |
| رمز التحديث: | 20240610 |
| مُعرف محوري في PubMed: | PMC10843625 |
| DOI: | 10.1016/j.cell.2023.11.031 |
| PMID: | 38176410 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4172 |
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| DOI: | 10.1016/j.cell.2023.11.031 |