Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans

被引：58

作者：

Bermejo-Jambrina, Marta ^{[1
]}

Eder, Julia ^{[1
]}

Kaptein, Tanja M. ^{[1
]}

vanHamme, John L. ^{[1
]}

Helgers, Leanne C. ^{[1
]}

Vlaming, Killian E. ^{[1
]}

Brouwer, Philip J. M. ^{[2
]}

vanNuenen, Ad C. ^{[1
]}

Spaargaren, Marcel ^{[3
]}

deBree, Godelieve J. ^{[4
]}

Nijmeijer, Bernadien M. ^{[1
]}

Kootstra, Neeltje A. ^{[1
]}

vanGils, Marit J. ^{[2
]}

Sanders, Rogier W. ^{[2
,5
]}

Geijtenbeek, Teunis B. H. ^{[1
]}

机构：

[1] Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Inst Infect & Immun, Dept Expt Immunol, Amsterdam, Netherlands

[2] Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Inst Infect & Immun, Dept Med Microbiol, Amsterdam, Netherlands

[3] Univ Amsterdam, Amsterdam Univ Med Ctr, Lymphoma & Myeloma Ctr Amsterdam LYMMCARE, Canc Ctr Amsterdam CCA,Dept Pathol, Amsterdam, Netherlands

[4] Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Inst Infect & Immun, Dept Internal Med, Amsterdam, Netherlands

[5] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

来源：

EMBO JOURNAL | 2021年 / 40卷 / 20期

基金：

比尔及梅琳达.盖茨基金会; 欧洲研究理事会;

关键词：

dendritic cells; epithelial cells; Heparan sulfate proteoglycans; low molecular weight heparins; SARS-CoV-2; HUMAN-IMMUNODEFICIENCY-VIRUS; CORONAVIRUS SPIKE PROTEIN; HEPATITIS-C VIRUS; SARS CORONAVIRUS; EPITHELIAL-CELLS; DC-SIGN; BINDING; RECEPTOR; ATTACHMENT; SYNDECAN-1;

D O I：

10.15252/embj.2020106765

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2, and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.

引用

页数：16

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