首页|Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells

Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells

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The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has caused a global economic and health crisis.Recently,plasma levels of galectin-9(Gal-9),a β-galactoside-binding lectin involved in immune regulation and viral immunopatho-genesis,were reported to be elevated in the setting of severe COVID-19 disease.However,the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated.In this study,we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells(AECs),including immortalized AECs and primary AECs cultured at the air-liquid interface.Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2(ACE2)-dependent manner,enhancing the binding of the viral spike protein to ACE2.Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs,including the IL-6,IL-8,IL-17,EIF2,and TNFα signaling pathways.Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.

SARS-CoV-2galectin-9inflammationairway epithelial cells

Li Du、Mohamed S.Bouzidi、Akshay Gala、Fred Deiter、Jean-No?l Billaud、Stephen T.Yeung、Prerna Dabral、Jing Jin、Graham Simmons、Zain Y.Dossani、Toshiro Niki、Lishomwa C.Ndhlovu、John R.Greenland、Satish K.Pillai

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Vitalant Research Institute,San Francisco,CA 94105,USA

Department of Laboratory Medicine,University of California,San Francisco,CA 94143-0134,USA

Department of Medicine,University of California,San Francisco,CA 94143-0410,USA

Veterans Affairs Health Care System,San Francisco,CA 94121,USA

QIAGEN Digital Insights,Redwood City,CA 94063,USA

Division of Infectious Diseases,Department of Medicine,Weill Cornell Medicine,New York,NY 10021,USA

Department of Immunology,Kagawa University,Kagawa 760-0016,Japan

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Program for Breakthrough Biomedical ResearchSandler FoundationNational Institutes of HealthUniversity of California San Francisco-Gladstone Institute of Virology&Immunology Center for AIDS Research

R01MH112457P30 AI027763

2023

10.1093/jmcb/mjad030

分子细胞生物学报(英文版)
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

分子细胞生物学报(英文版)

CSTPCDCSCD
影响因子：0.595
ISSN：1673-520X
年,卷(期)：2023.15(4)
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