Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

被引：1390

作者：

Cantuti-Castelvetri, Ludovico ^{[1
,2
]}

Ojha, Ravi ^{[3
]}

Pedro, Liliana D. ^{[1
,2
]}

Djannatian, Minou ^{[1
,2
]}

Franz, Jonas ^{[4
,5
,6
]}

Kuivanen, Suvi ^{[7
]}

van der Meer, Franziska ^{[4
]}

Kallio, Katri ^{[3
]}

Kaya, Tugberk ^{[1
,2
,8
]}

Anastasina, Maria ^{[3
,9
]}

Smura, Teemu ^{[7
]}

Levanov, Lev ^{[7
]}

Szirovicza, Leonora ^{[7
]}

Tobi, Allan ^{[10
]}

Kallio-Kokko, Hannimari ^{[11
,12
]}

Osterlund, Pamela ^{[13
]}

Joensuu, Merja ^{[14
]}

Meunier, Frederic A. ^{[14
]}

Butcher, Sarah J. ^{[3
,9
]}

Winkler, Martin Sebastian ^{[15
]}

Mollenhauer, Brit ^{[16
,17
]}

Helenius, Ari ^{[18
]}

Gokce, Ozgun ^{[8
]}

Teesalu, Tambet ^{[3
,20
,21
,22
]}

Hepojoki, Jussi ^{[5
,23
]}

Vapalahti, Olli ^{[7
,11
,12
,24
]}

Stadelmann, Christine ^{[4
]}

Balistreri, Giuseppe ^{[3
,19
]}

Simons, Mikael ^{[1
,2
,25
]}

机构：

[1] Tech Univ Munich, Inst Neuronal Cell Biol, Munich, Germany

[2] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[3] Univ Helsinki, Mol & Integrat Biosci Res Program, Fac Biol & Environm Sci, Helsinki, Finland

[4] Univ Med Ctr Gottingen, Dept Neuropathol, Gottingen, Germany

[5] Univ Gottingen, Campus Inst Dynam Biol Networks, Gottingen, Germany

[6] Max Planck Inst Expt Med, Gottingen, Germany

[7] Univ Helsinki, Dept Virol, Medicum, Helsinki, Finland

[8] Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany

[9] Univ Helsinki, Inst Biotechnol, Helsinki Inst Life Sci, Helsinki, Finland

[10] Univ Tartu, Inst Biomed & Translat Med, Lab Canc Biol, Tartu, Estonia

[11] Univ Helsinki, Dept Virol, Helsinki, Finland

[12] Helsinki Univ Hosp, Helsinki, Finland

[13] Finnish Inst Hlth & Welf THL, Dept Hlth Secur, Helsinki, Finland

[14] Univ Queensland, Queensland Brain Inst, Clem Jones Ctr Ageing Dementia Res, Brisbane, Qld, Australia

[15] Univ Med Ctr Gottingen, Dept Anesthesiol & Intens Care Med, Gottingen, Germany

[16] Univ Med Ctr Gottingen, Dept Neurol, Gottingen, Germany

[17] Paracelsus Elena Klin Kassel, Kassel, Germany

[18] Swiss Fed Inst Technol, Inst Biochem, Zurich, Switzerland

[19] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[20] Sanford Burnham Prebys Med Discovery Inst, Canc Res Ctr, La Jolla, CA USA

[21] Univ Calif Santa Barbara, Ctr Nanomed, Santa Barbara, CA 93106 USA

[22] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA

[23] Univ Zurich, Vetsuisse Fac, Inst Vet Pathol, Zurich, Switzerland

[24] Univ Helsinki, Dept Vet Biosci, Helsinki, Finland

[25] Munich Cluster Syst Neurol SyNergy, Munich, Germany

来源：

SCIENCE | 2020年 / 370卷 / 6518期

基金：

澳大利亚研究理事会; 英国医学研究理事会; 芬兰科学院; 英国惠康基金; 欧洲研究理事会;

关键词：

VIRUS; PROTEIN; IMAGE; SPIKE;

D O I：

10.1126/science.abd2985

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

引用

页码：856 / +

页数：40

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