Human transferrin receptor can mediate SARS-CoV-2 infection.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 121 (2024-03-05), Heft 10, S. 1-40
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Human transferrin receptor can mediate SARS-CoV-2 infection.
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Autor/in / Beteiligte Person: | Liao, Zhiyi ; Wang, Chaoming ; Tang, Xiaopeng ; Yang, Mengli ; Duan, Zilei ; Liu, Lei ; Lu, Shuaiyao ; Ma, Lei ; Cheng, Ruomei ; Wang, Gan ; Liu, Hongqi ; Yang, Shuo ; Xu, Jingwen ; Tadese, Dawit Adisu ; Mwangi, James ; Kamau, Peter Muiruri ; Zhang, Zhiye ; Yang, Lian ; Liao, Guoyang ; Zhao, Xudong |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 121 (2024-03-05), Heft 10, S. 1-40 |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.2317026121 |
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