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Lrp1 is a host entry factor for Rift Valley fever virus.
Ganaie, Safder S; Schwarz, Madeline M; McMillen, Cynthia M; Price, David A; Feng, Annie X; Albe, Joseph R; Wang, Wenjie; Miersch, Shane; Orvedahl, Anthony; Cole, Aidan R; Sentmanat, Monica F; Mishra, Nawneet; Boyles, Devin A; Koenig, Zachary T; Kujawa, Michael R; Demers, Matthew A; Hoehl, Ryan M; Moyle, Austin B; Wagner, Nicole D; Stubbs, Sarah H; Cardarelli, Lia; Teyra, Joan; McElroy, Anita; Gross, Michael L; Whelan, Sean P J; Doench, John; Cui, Xiaoxia; Brett, Tom J; Sidhu, Sachdev S; Virgin, Herbert W; Egawa, Takeshi; Leung, Daisy W; Amarasinghe, Gaya K; Hartman, Amy L.
Afiliação
  • Ganaie SS; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Schwarz MM; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • McMillen CM; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Price DA; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Feng AX; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Albe JR; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Wang W; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Miersch S; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Orvedahl A; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Cole AR; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Sentmanat MF; Genome Engineering and iPSC Center (GEiC), Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Mishra N; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Boyles DA; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Koenig ZT; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kujawa MR; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Demers MA; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Hoehl RM; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Moyle AB; Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA.
  • Wagner ND; Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA.
  • Stubbs SH; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Cardarelli L; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Teyra J; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • McElroy A; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, Division of Pediatric Infectious Disease, University of Pittsburgh, Pittsburgh, PA, USA.
  • Gross ML; Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA.
  • Whelan SPJ; Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO, USA.
  • Doench J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cui X; Genome Engineering and iPSC Center (GEiC), Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Brett TJ; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Sidhu SS; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Virgin HW; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Current address: Vir Biotechnology, San Francisco, CA, USA.
  • Egawa T; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Leung DW; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Amarasinghe GK; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. Electronic address: gamarasinghe@wustl.edu.
  • Hartman AL; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: hartman2@pitt.edu.
Cell ; 184(20): 5163-5178.e24, 2021 09 30.
Article em En | MEDLINE | ID: mdl-34559985
ABSTRACT
Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFV entry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorly defined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-related protein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associated protein (RAP) as critical host factors for RVFV infection. RVFV Gn directly binds to specific Lrp1 clusters and is glycosylation independent. Exogenous addition of murine RAP domain 3 (mRAPD3) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse cell lines. Mice treated with mRAPD3 and infected with pathogenic RVFV are protected from disease and death. A mutant mRAPD3 that binds Lrp1 weakly failed to protect from RVFV infection. Together, these data support Lrp1 as a host entry factor for RVFV infection and define a new target to limit RVFV infections.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Febre do Vale do Rift / Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade / Internalização do Vírus / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Febre do Vale do Rift / Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade / Internalização do Vírus / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos