HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.

Abstract

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

• Authors: Congwen Wei, Luming Wan, Qiulin Yan, Xiaolin Wang, Jun Zhang, Xiaopan Yang, Yanhong Zhang, Chen Fan, Dongyu Li, Yongqiang Deng, Jin Sun, Jing Gong, Xiaoli Yang, Yufei Wang, Xuejun Wang, Jianmin Li, Huan Yang, Huilong Li, Zhe Zhang, Rong Wang, Peng Du, Yulong Zong, Feng Yin, Wanchuan Zhang, Nan Wang, Yumeng Peng, Haotian Lin, Jiangyue Feng, Chengfeng Qin, Wei Chen, Qi Gao, Rui Zhang, Yuan Cao, Hui Zhong
• Journal: Nature metabolism (Nat Metab) Vol. 2 Issue 12 Pg. 1391-1400 (12 2020) ISSN: 2522-5812 [Electronic] Germany
• PMID: 33244168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, HDL
• Receptors, Virus
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Spike Glycoprotein, Coronavirus
• Cholesterol

Topics

• COVID-19 (metabolism, virology)
• Cell Line
• Cholesterol (metabolism)
• Disease Susceptibility
• Host-Pathogen Interactions
• Humans
• Lipoproteins, HDL (metabolism)
• Protein Binding
• Receptors, Virus
• SARS-CoV-2 (physiology)
• Scavenger Receptors, Class B (metabolism)
• Spike Glycoprotein, Coronavirus (metabolism)
• Viral Tropism
• Virus Attachment
• Virus Internalization