Author:
Cantuti-Castelvetri Ludovico,Ojha Ravi,Pedro Liliana D.,Djannatian Minou,Franz Jonas,Kuivanen Suvi,Kallio Katri,Kaya Tuğberk,Anastasina Maria,Smura Teemu,Levanov Lev,Szirovicza Leonora,Tobi Allan,Kallio-Kokko Hannimari,Österlund Pamela,Joensuu Merja,Meunier Frédéric A.,Butcher Sarah,Winkler Martin Sebastian,Mollenhauer Brit,Helenius Ari,Gokce Ozgun,Teesalu Tambet,Hepojoki Jussi,Vapalahti Olli,Stadelmann Christine,Balistreri Giuseppe,Simons Mikael
Abstract
SUMMARYThe 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
80 articles.
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