Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system
Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system
SUMMARY The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ3-5. Here, we found that the cellular receptor neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected NRP1-positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection was detected particularly within NRP1-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.
Kallio Katri、Teesalu Tambet、Kuivanen Suvi、Butcher Sarah、Cantuti-Castelvetri Ludovico、Franz Jonas、Winkler Martin Sebastian、Smura Teemu、Szirovicza Leonora、Helenius Ari、Gokce Ozgun、Hepojoki Jussi、Vapalahti Olli、Meunier Fr¨|d¨|ric A.、Levanov Lev、Simons Mikael、Djannatian Minou、Pedro Liliana D.、Balistreri Giuseppe、?sterlund Pamela、Kaya Tu?berk、Kallio-Kokko Hannimari、Mollenhauer Brit、Anastasina Maria、Ojha Ravi、Tobi Allan、Stadelmann Christine、Joensuu Merja
Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of HelsinkiFaculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki||Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute||Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of CaliforniaUniversity of Helsinki, Medicum, Department of VirologyFaculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki||Helsinki Institute of Life Sciences-Institute of Biotechnology, University of HelsinkiInstitute of Neuronal Cell Biology, Technical University Munich||German Center for Neurodegenerative Diseases (DZNE)Department of Neuropathology, University Medical Center G?ttingenDepartment of Anesthesiology and Intensive Care Medicine, University Medical Center G?ttingenUniversity of Helsinki, Medicum, Department of VirologyUniversity of Helsinki, Medicum, Department of VirologyInstitute of Biochemistry, ETH Z¨1richInstitute for Stroke and Dementia Research (ISD), University Hospital||Munich Cluster of Systems Neurology (SyNergy)University of Helsinki, Medicum, Department of Virology||Institute of Veterinary Pathology, Vetsuisse Faculty, University of Z¨1richUniversity of Helsinki, Medicum, Department of Virology||University of Helsinki and Helsinki University Hospital, Department of Virology||Dept of Veterinary Biosciences, University of HelsinkiClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandUniversity of Helsinki, Medicum, Department of VirologyInstitute of Neuronal Cell Biology, Technical University Munich||German Center for Neurodegenerative Diseases (DZNE)||Munich Cluster of Systems Neurology (SyNergy)Institute of Neuronal Cell Biology, Technical University Munich||German Center for Neurodegenerative Diseases (DZNE)Institute of Neuronal Cell Biology, Technical University Munich||German Center for Neurodegenerative Diseases (DZNE)Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of HelsinkiDepartment of Health Security, Finnish Institute for Health and Welfare (THL)Institute of Neuronal Cell Biology, Technical University Munich||German Center for Neurodegenerative Diseases (DZNE)||Institute for Stroke and Dementia Research (ISD), University HospitalUniversity of Helsinki and Helsinki University Hospital, Department of VirologyDepartment of Neurology, University Medical Center G?ttingen, G?ttingen, Germany & Paracelsus-Elena-Klinik KasselFaculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki||Helsinki Institute of Life Sciences-Institute of Biotechnology, University of HelsinkiFaculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of HelsinkiLaboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of TartuDepartment of Neuropathology, University Medical Center G?ttingenClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland
基础医学神经病学、精神病学微生物学
Kallio Katri,Teesalu Tambet,Kuivanen Suvi,Butcher Sarah,Cantuti-Castelvetri Ludovico,Franz Jonas,Winkler Martin Sebastian,Smura Teemu,Szirovicza Leonora,Helenius Ari,Gokce Ozgun,Hepojoki Jussi,Vapalahti Olli,Meunier Fr¨|d¨|ric A.,Levanov Lev,Simons Mikael,Djannatian Minou,Pedro Liliana D.,Balistreri Giuseppe,?sterlund Pamela,Kaya Tu?berk,Kallio-Kokko Hannimari,Mollenhauer Brit,Anastasina Maria,Ojha Ravi,Tobi Allan,Stadelmann Christine,Joensuu Merja.Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system[EB/OL].(2025-03-28)[2025-05-09].https://www.biorxiv.org/content/10.1101/2020.06.07.137802.点此复制
评论