Lrp1 is a host entry factor for Rift Valley fever virus.

Autor:	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.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2021 Sep 30; Vol. 184 (20), pp. 5163-5178.e24. Date of Electronic Publication: 2021 Sep 23.
DOI:	10.1016/j.cell.2021.09.001
Abstrakt:	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 (mRAP D3 ) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse cell lines. Mice treated with mRAP D3 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. Competing Interests: Declaration of interests H.W.V. is a founder of Casma Therapeutics and pierianDx and is employed by Vir Biotechnology. None of these companies funded the work reported here. Invention disclosures for method of use for Lrp1 interaction with RVFV Gn (G.K.A., A.L.H., D.W.L., H.W.V., and S.S.G.) and for the use of anti-Lrp1 antibodies by U Toronto (S.S.S., S.M., and G.K.A.) have been filed. Inclusion and diversity We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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