Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

被引：126

作者：

Chu, Hin ^{[1
,2
]}

Hu, Bingjie ^{[2
]}

Huang, Xiner ^{[2
]}

Chai, Yue ^{[2
]}

Zhou, Dongyan ^{[2
]}

Wang, Yixin ^{[2
]}

Shuai, Huiping ^{[2
]}

Yang, Dong ^{[2
]}

Hou, Yuxin ^{[2
]}

Zhang, Xi ^{[2
]}

Yuen, Terrence Tsz-Tai ^{[2
]}

Cai, Jian-Piao ^{[2
]}

Zhang, Anna Jinxia ^{[1
,2
]}

Zhou, Jie ^{[1
,2
]}

Yuan, Shuofeng ^{[1
,2
,3
,4
]}

To, Kelvin Kai-Wang ^{[5
]}

Chan, Ivy Hau-Yee ^{[5
]}

Sit, Ko-Yung ^{[5
]}

Foo, Dominic Chi-Chung ^{[5
]}

Wong, Ian Yu-Hong ^{[5
]}

Ng, Ada Tsui-Lin ^{[5
]}

Cheung, Tan To ^{[5
]}

Law, Simon Ying-Kit ^{[5
]}

Au, Wing-Kuk ^{[5
]}

Brindley, Melinda A. ^{[6
]}

Chen, Zhiwei ^{[1
,2
,3
]}

Kok, Kin-Hang ^{[1
,2
,3
]}

Chan, Jasper Fuk-Woo ^{[1
,2
,3
,4
,7
]}

Yuen, Kwok-Yung ^{[1
,2
,3
,4
,7
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, Li Ka Shing Fac Med, Carol Yu Ctr Infect, Pokfulam, Hong Kong, Peoples R China

[4] Queen Mary Hosp, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China

[5] Univ Hong Kong, Li Ka Shing Fac Med, Dept Surg, Pokfulam, Hong Kong, Peoples R China

[6] Univ Georgia, Dept Infect Dis, Dept Populat Hlth, Coll Vet Med, Athens, GA 30602 USA

[7] Univ Hong Kong, Hainan Med Univ Univ Hong Kong Joint Lab Trop Inf, Pokfulam, Hong Kong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; SIALIC-ACID; HEPARAN-SULFATE; CELL ENTRY; SPIKE; ATTACHMENT; RECEPTOR; MOLECULE; PROTEIN;

D O I：

10.1038/s41467-020-20457-w

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：

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs. Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

引用

页数：15

共 58 条

[1] The proximal origin of SARS-CoV-2 [J].

Andersen, Kristian G. ;

Rambaut, Andrew ;

Lipkin, W. Ian ;

Holmes, Edward C. ;

Garry, Robert F. .

NATURE MEDICINE, 2020, 26 (04) :450-452

[2]

[Anonymous], 2015, MICROBIOL MOL BIOL R, DOI DOI 10.1016/J.ANTIVIRAL.2015.01.011

[3]

[Anonymous], 2010, VIROLOGY, DOI DOI 10.1016/J.JVIROMET.2010.08.006

[4]

[Anonymous], 2004, P NATL ACAD SCI USA, DOI DOI 10.1128/MMBR.68.1.132-153.2004

[5]

[Anonymous], 2011, ANTIVIR RES, DOI DOI 10.1016/J.VIROL.2011.02.020

[6]

[Anonymous], 1996, ANTIVIR RES, DOI DOI 10.1128/JVI.70.8.5634-5637.1996

[7]

[Anonymous], 1998, SCIENCE, DOI DOI 10.1016/S0140-6736(97)11212-0

[8]

[Anonymous], 1999, NAT MED, DOI DOI 10.1016/S0092-8674(00)80058-6

[9]

[Anonymous], 2020, CELL DISCOV, DOI DOI 10.1016/J.ANTIVIRAL.2020.104873

[10]

[Anonymous], 2020, NAT STRUCT MOL BIOL, DOI DOI 10.1016/S2666-5247(20)30004-5

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