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

Author:

Chu HinORCID,Hu Bingjie,Huang XinerORCID,Chai Yue,Zhou Dongyan,Wang Yixin,Shuai Huiping,Yang Dong,Hou Yuxin,Zhang Xi,Yuen Terrence Tsz-Tai,Cai Jian-Piao,Zhang Anna Jinxia,Zhou JieORCID,Yuan Shuofeng,To Kelvin Kai-WangORCID,Chan Ivy Hau-Yee,Sit Ko-Yung,Foo Dominic Chi-ChungORCID,Wong Ian Yu-Hong,Ng Ada Tsui-Lin,Cheung Tan To,Law Simon Ying-KitORCID,Au Wing-Kuk,Brindley Melinda A.ORCID,Chen ZhiweiORCID,Kok Kin-HangORCID,Chan Jasper Fuk-WooORCID,Yuen Kwok-YungORCID

Abstract

AbstractUnderstanding 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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