RT Journal Article
SR Electronic
T1 Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.07.137802
DO 10.1101/2020.06.07.137802
A1 Cantuti-Castelvetri, Ludovico
A1 Ojha, Ravi
A1 Pedro, Liliana D.
A1 Djannatian, Minou
A1 Franz, Jonas
A1 Kuivanen, Suvi
A1 Kallio, Katri
A1 Kaya, Tuğberk
A1 Anastasina, Maria
A1 Smura, Teemu
A1 Levanov, Lev
A1 Szirovicza, Leonora
A1 Tobi, Allan
A1 Kallio-Kokko, Hannimari
A1 Österlund, Pamela
A1 Joensuu, Merja
A1 Meunier, Frédéric A.
A1 Butcher, Sarah
A1 Winkler, Martin Sebastian
A1 Mollenhauer, Brit
A1 Helenius, Ari
A1 Gokce, Ozgun
A1 Teesalu, Tambet
A1 Hepojoki, Jussi
A1 Vapalahti, Olli
A1 Stadelmann, Christine
A1 Balistreri, Giuseppe
A1 Simons, Mikael
YR 2020
UL http://biorxiv.org/content/early/2020/07/15/2020.06.07.137802.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.