Human transferrin receptor can mediate SARS-CoV-2 infection

• 成果类型: Article
• 署名作者: 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; Peng, Xiaozhong; Lai, Ren
• 署名单位: Chinese Academy of Sciences; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Qingdao University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Medical Biology - CAMS; Sichuan University; Chinese Academy of Sciences; Kunming Institute of Botany, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13725
• DOI: 10.1073/pnas.2317026121
• 发表日期: 2024-03-05
• 关键词: cellular receptor; CORONAVIRUS; entry; iron; virus; identification; parvoviruses; ferroptosis; Covid-19; binding

摘要

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 (K-D similar to 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.