Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes.

Journal

Signal transduction and targeted therapy
ISSN: 2059-3635
Titre abrégé: Signal Transduct Target Ther
Pays: England
ID NLM: 101676423

Informations de publication

Date de publication:
14 Feb 2024
Historique:
received: 29 08 2023
accepted: 23 01 2024
revised: 18 12 2023
medline: 15 2 2024
pubmed: 15 2 2024
entrez: 14 2 2024
Statut: epublish

Résumé

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells. To address this question, we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1 (ASGR1) promoted SARS-CoV-2 pseudovirus infection of HeLa cells. In Huh-7 cells, simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells, both of which barely expressed ACE2, SARS-CoV-2 pseudovirus could successfully establish an infection. However, after treatment with ASGR1 antibody or siRNA targeting ASGR1, the infection rate significantly dropped, suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism. We confirmed that ASGR1 could interact with Spike protein, which depends on receptor binding domain (RBD) and N-terminal domain (NTD). Finally, we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells. After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA, the infection efficiency of the live virus decreased significantly. Collectively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

Identifiants

DOI: 10.1038/s41392-024-01754-y PMID: 38355848
pubmed: 38355848
doi: 10.1038/s41392-024-01754-y
pii: 10.1038/s41392-024-01754-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

42

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82041001
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31771484
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 92169112

Informations de copyright

© 2024. The Author(s).

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Auteurs

Xinyi Yang (X)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Xu Zheng (X)

Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.

Yuqi Zhu (Y)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Xiaying Zhao (X)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Jun Liu (J)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Jiangna Xun (J)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.
Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Songhua Yuan (S)

Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Jun Chen (J)

Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Hanyu Pan (H)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Jinlong Yang (J)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Jing Wang (J)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Zhimin Liang (Z)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Xiaoting Shen (X)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Yue Liang (Y)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Qinru Lin (Q)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Huitong Liang (H)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Min Li (M)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Fei Peng (F)

Changzheng Hospital, Naval Medical University, Shanghai, China.

Daru Lu (D)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China.

Jianqing Xu (J)

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Hongzhou Lu (H)

Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Infectious Diseases and Nursing Research Institution, National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong, China.

Shibo Jiang (S)

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Ping Zhao (P)

Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China. pnzhao@163.com.

Huanzhang Zhu (H)

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Yiwu Research Institute, Fudan University, Shanghai, China. hzzhu@fudan.edu.cn.
ORCID: 0000-0001-5797-0292

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