tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Mar 5;121(10):e2317026121.
doi: 10.1073/pnas.2317026121. Epub 2024 Feb 26. Human transferrin receptor can mediate SARS-CoV-2 infection
Zhiyi Liao[SUP] #[/SUP][SUP] 1 2 [/SUP], Chaoming Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Xiaopeng Tang[SUP] #[/SUP][SUP] 1 3 [/SUP], Mengli Yang[SUP] #[/SUP][SUP] 4 [/SUP], Zilei Duan[SUP] #[/SUP][SUP] 1 [/SUP], Lei Liu[SUP] #[/SUP][SUP] 5 [/SUP], Shuaiyao Lu[SUP] #[/SUP][SUP] 4 [/SUP], Lei Ma[SUP] #[/SUP][SUP] 4 [/SUP], Ruomei Cheng[SUP] 1 [/SUP], Gan Wang[SUP] 1 [/SUP], Hongqi Liu[SUP] 4 [/SUP], Shuo Yang[SUP] 1 2 [/SUP], Jingwen Xu[SUP] 4 [/SUP], Dawit Adisu Tadese[SUP] 1 2 [/SUP], James Mwangi[SUP] 1 2 [/SUP], Peter Muiruri Kamau[SUP] 1 2 [/SUP], Zhiye Zhang[SUP] 1 [/SUP], Lian Yang[SUP] 6 [/SUP], Guoyang Liao[SUP] 4 [/SUP], Xudong Zhao[SUP] 5 [/SUP], Xiaozhong Peng[SUP] 4 [/SUP], Ren Lai[SUP] 1 [/SUP]
Affiliations
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[SUB]D[/SUB] ~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.
Keywords: SARS-CoV-2; alternative receptors; interaction; spike; transferrin receptor.
. 2024 Mar 5;121(10):e2317026121.
doi: 10.1073/pnas.2317026121. Epub 2024 Feb 26. Human transferrin receptor can mediate SARS-CoV-2 infection
Zhiyi Liao[SUP] #[/SUP][SUP] 1 2 [/SUP], Chaoming Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Xiaopeng Tang[SUP] #[/SUP][SUP] 1 3 [/SUP], Mengli Yang[SUP] #[/SUP][SUP] 4 [/SUP], Zilei Duan[SUP] #[/SUP][SUP] 1 [/SUP], Lei Liu[SUP] #[/SUP][SUP] 5 [/SUP], Shuaiyao Lu[SUP] #[/SUP][SUP] 4 [/SUP], Lei Ma[SUP] #[/SUP][SUP] 4 [/SUP], Ruomei Cheng[SUP] 1 [/SUP], Gan Wang[SUP] 1 [/SUP], Hongqi Liu[SUP] 4 [/SUP], Shuo Yang[SUP] 1 2 [/SUP], Jingwen Xu[SUP] 4 [/SUP], Dawit Adisu Tadese[SUP] 1 2 [/SUP], James Mwangi[SUP] 1 2 [/SUP], Peter Muiruri Kamau[SUP] 1 2 [/SUP], Zhiye Zhang[SUP] 1 [/SUP], Lian Yang[SUP] 6 [/SUP], Guoyang Liao[SUP] 4 [/SUP], Xudong Zhao[SUP] 5 [/SUP], Xiaozhong Peng[SUP] 4 [/SUP], Ren Lai[SUP] 1 [/SUP]
Affiliations
- PMID: 38408250
- DOI: 10.1073/pnas.2317026121
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[SUB]D[/SUB] ~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.
Keywords: SARS-CoV-2; alternative receptors; interaction; spike; transferrin receptor.