Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1.

Autor:	Schwarz MM; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213.; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213., Price DA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110., Ganaie SS; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Feng A; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Mishra N; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Hoehl RM; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213., Fatma F; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Stubbs SH; Department of Microbiology, Harvard Medical School, Boston, MA, 02115., Whelan SPJ; Department of Molecular Microbiology, Washington University, St. Louis, MO, 63110., Cui X; Genome Engineering & Stem Cell Center (GESC@MGI), Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Egawa T; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Leung DW; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Amarasinghe GK; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110., Hartman AL; Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213.; Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Aug 16; Vol. 119 (33), pp. e2204706119. Date of Electronic Publication: 2022 Aug 08.
DOI:	10.1073/pnas.2204706119
Abstrakt:	Oropouche orthobunyavirus (OROV; Peribunyaviridae ) is a mosquito-transmitted virus that causes widespread human febrile illness in South America, with occasional progression to neurologic effects. Host factors mediating the cellular entry of OROV are undefined. Here, we show that OROV uses the host protein low-density lipoprotein-related protein 1 (Lrp1) for efficient cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. In addition, chimeric vesicular stomatitis virus (VSV) expressing OROV glycoproteins (VSV-OROV) bound to the Lrp1 ectodomain in vitro. Furthermore, we demonstrate the biological relevance of the OROV-Lrp1 interaction in a proof-of-concept mouse study in which treatment of mice with RAP at the time of infection reduced tissue viral load and promoted survival from an otherwise lethal infection. These results with OROV, along with the recent finding of Lrp1 as an entry factor for Rift Valley fever virus, highlight the broader significance of Lrp1 in cellular infection by diverse bunyaviruses. Shared strategies for entry, such as the critical function of Lrp1 defined here, provide a foundation for the development of pan-bunyaviral therapeutics.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu