tetano
Editor, Senior Moderator
Nat Metab
. 2020 Nov 26.
doi: 10.1038/s42255-020-00324-0. Online ahead of print.
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry
Congwen Wei[SUP] 1 [/SUP], Luming Wan[SUP] 1 [/SUP], Qiulin Yan[SUP] 1 2 [/SUP], Xiaolin Wang[SUP] 1 [/SUP], Jun Zhang[SUP] 1 [/SUP], Xiaopan Yang[SUP] 1 [/SUP], Yanhong Zhang[SUP] 1 [/SUP], Chen Fan[SUP] 3 [/SUP], Dongyu Li[SUP] 1 [/SUP], Yongqiang Deng[SUP] 4 [/SUP], Jin Sun[SUP] 1 [/SUP], Jing Gong[SUP] 1 2 [/SUP], Xiaoli Yang[SUP] 5 [/SUP], Yufei Wang[SUP] 5 [/SUP], Xuejun Wang[SUP] 6 [/SUP], Jianmin Li[SUP] 1 [/SUP], Huan Yang[SUP] 1 [/SUP], Huilong Li[SUP] 1 [/SUP], Zhe Zhang[SUP] 1 [/SUP], Rong Wang[SUP] 1 [/SUP], Peng Du[SUP] 1 [/SUP], Yulong Zong[SUP] 7 [/SUP], Feng Yin[SUP] 7 [/SUP], Wanchuan Zhang[SUP] 8 [/SUP], Nan Wang[SUP] 8 [/SUP], Yumeng Peng[SUP] 1 [/SUP], Haotian Lin[SUP] 1 [/SUP], Jiangyue Feng[SUP] 1 [/SUP], Chengfeng Qin[SUP] 4 [/SUP], Wei Chen[SUP] 1 [/SUP], Qi Gao[SUP] 9 [/SUP], Rui Zhang[SUP] 10 [/SUP], Yuan Cao[SUP] 11 [/SUP], Hui Zhong[SUP] 12 [/SUP]
Affiliations
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.
. 2020 Nov 26.
doi: 10.1038/s42255-020-00324-0. Online ahead of print.
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry
Congwen Wei[SUP] 1 [/SUP], Luming Wan[SUP] 1 [/SUP], Qiulin Yan[SUP] 1 2 [/SUP], Xiaolin Wang[SUP] 1 [/SUP], Jun Zhang[SUP] 1 [/SUP], Xiaopan Yang[SUP] 1 [/SUP], Yanhong Zhang[SUP] 1 [/SUP], Chen Fan[SUP] 3 [/SUP], Dongyu Li[SUP] 1 [/SUP], Yongqiang Deng[SUP] 4 [/SUP], Jin Sun[SUP] 1 [/SUP], Jing Gong[SUP] 1 2 [/SUP], Xiaoli Yang[SUP] 5 [/SUP], Yufei Wang[SUP] 5 [/SUP], Xuejun Wang[SUP] 6 [/SUP], Jianmin Li[SUP] 1 [/SUP], Huan Yang[SUP] 1 [/SUP], Huilong Li[SUP] 1 [/SUP], Zhe Zhang[SUP] 1 [/SUP], Rong Wang[SUP] 1 [/SUP], Peng Du[SUP] 1 [/SUP], Yulong Zong[SUP] 7 [/SUP], Feng Yin[SUP] 7 [/SUP], Wanchuan Zhang[SUP] 8 [/SUP], Nan Wang[SUP] 8 [/SUP], Yumeng Peng[SUP] 1 [/SUP], Haotian Lin[SUP] 1 [/SUP], Jiangyue Feng[SUP] 1 [/SUP], Chengfeng Qin[SUP] 4 [/SUP], Wei Chen[SUP] 1 [/SUP], Qi Gao[SUP] 9 [/SUP], Rui Zhang[SUP] 10 [/SUP], Yuan Cao[SUP] 11 [/SUP], Hui Zhong[SUP] 12 [/SUP]
Affiliations
- PMID: 33244168
- DOI: 10.1038/s42255-020-00324-0
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.