Human transferrin receptor can mediate SARS-CoV-2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 10 vom: 05. März, Seite e2317026121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liao, Zhiyi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2317026121 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368982092 |
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| 520 | |a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Chaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Xiaopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Mengli |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Zilei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shuaiyao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ruomei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Gan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hongqi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Shuo |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jingwen |e verfasserin |4 aut | |
| 700 | 1 | |a Tadese, Dawit Adisu |e verfasserin |4 aut | |
| 700 | 1 | |a Mwangi, James |e verfasserin |4 aut | |
| 700 | 1 | |a Kamau, Peter Muiruri |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhiye |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Lian |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Guoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Xiaozhong |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Ren |e verfasserin |4 aut | |
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