tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2026 Feb 3;11(1):42.
doi: 10.1038/s41392-025-02551-x.
Inducible CD147 up-regulation boosts extended SARS-CoV-2 infection triggering severe COVID-19 independent of ACE2
Ke Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Peng Lin[SUP] #[/SUP][SUP] 1 2 [/SUP], Ruo Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Qiang Huang[SUP] #[/SUP][SUP] 2 3 [/SUP], Yizhen Zhao[SUP] #[/SUP][SUP] 4 [/SUP], Lei Zhang[SUP] 4 [/SUP], Yongxiang Zhao[SUP] 5 [/SUP], Liping Zhong[SUP] 5 [/SUP], Ke Xu[SUP] 6 [/SUP], Linlin Bao[SUP] 7 [/SUP], Youchun Wang[SUP] 8 [/SUP], Chuan Qin[SUP] 7 [/SUP], Guizhen Wu[SUP] 6 [/SUP], Hai Zhang[SUP] 1 2 [/SUP], Jiejie Geng[SUP] 1 2 [/SUP], Zheng Zhang[SUP] 1 2 [/SUP], Ding Wei[SUP] 1 2 [/SUP], Xiaochun Chen[SUP] 9 [/SUP], Hao Tang[SUP] 9 [/SUP], Liu Yang[SUP] 1 2 [/SUP], Xu Yang[SUP] 1 2 [/SUP], Xiuxuan Sun[SUP] 1 2 [/SUP], Rui Yao[SUP] 1 2 [/SUP], Ye Zhao[SUP] 1 2 [/SUP], Weijun Qin[SUP] 10 [/SUP], Zhiwei Yang[SUP] 11 [/SUP], Liang Chen[SUP] 12 13 [/SUP], Huijie Bian[SUP] 14 15 [/SUP], Zhi-Nan Chen[SUP] 16 17 [/SUP], Ping Zhu[SUP] 18 19 [/SUP]
Affiliations
The high mortality caused by severe COVID-19 poses great challenges to the public health. However, the underlying pathogenesis of severe cases remains unclear. Here, we find that SARS-CoV-2 infection boosts CD147 inducible up-regulation in the lung tissues of virus-infected rhesus macaques coupled with down-regulated membrane-bound ACE2, which conduces to extended virus infection and severe pathological lesions. Specifically, SARS-CoV-2 infection enhances the expression of transcriptional factor aryl hydrocarbon receptor and facilitates its nucleus translocation, which causes CD147 gene transcription and its up-regulation in protein level, thereby leading to virus susceptibility of the hosts and extended virus infection. Meanwhile, SARS-CoV-2 infection triggers immune imbalance of lung tissues by promoting cell death of CD4 + T cells and B cells and mediating abnormal cell-cell communications, especially for M2 macrophages. Meplazumab, a humanized anti-CD147 antibody, effectively inhibits virus entry and cytokine level, and restores immune balance in the lung tissues of virus-infected rhesus macaque model. Importantly, we further present the cryo-EM structure of CD147-spike complex, and identify five pairs of functional residues for their interaction, which could be interrupted by Meplazumab via steric hindrance effect. Our findings provide direct evidence for CD147-SARS-CoV-2 spike interaction and uncover the pathogenesis of severe COVID-19 caused by CD147-mediated extended virus infection.
. 2026 Feb 3;11(1):42.
doi: 10.1038/s41392-025-02551-x.
Inducible CD147 up-regulation boosts extended SARS-CoV-2 infection triggering severe COVID-19 independent of ACE2
Ke Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Peng Lin[SUP] #[/SUP][SUP] 1 2 [/SUP], Ruo Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Qiang Huang[SUP] #[/SUP][SUP] 2 3 [/SUP], Yizhen Zhao[SUP] #[/SUP][SUP] 4 [/SUP], Lei Zhang[SUP] 4 [/SUP], Yongxiang Zhao[SUP] 5 [/SUP], Liping Zhong[SUP] 5 [/SUP], Ke Xu[SUP] 6 [/SUP], Linlin Bao[SUP] 7 [/SUP], Youchun Wang[SUP] 8 [/SUP], Chuan Qin[SUP] 7 [/SUP], Guizhen Wu[SUP] 6 [/SUP], Hai Zhang[SUP] 1 2 [/SUP], Jiejie Geng[SUP] 1 2 [/SUP], Zheng Zhang[SUP] 1 2 [/SUP], Ding Wei[SUP] 1 2 [/SUP], Xiaochun Chen[SUP] 9 [/SUP], Hao Tang[SUP] 9 [/SUP], Liu Yang[SUP] 1 2 [/SUP], Xu Yang[SUP] 1 2 [/SUP], Xiuxuan Sun[SUP] 1 2 [/SUP], Rui Yao[SUP] 1 2 [/SUP], Ye Zhao[SUP] 1 2 [/SUP], Weijun Qin[SUP] 10 [/SUP], Zhiwei Yang[SUP] 11 [/SUP], Liang Chen[SUP] 12 13 [/SUP], Huijie Bian[SUP] 14 15 [/SUP], Zhi-Nan Chen[SUP] 16 17 [/SUP], Ping Zhu[SUP] 18 19 [/SUP]
Affiliations
- PMID: 41629286
- DOI: 10.1038/s41392-025-02551-x
The high mortality caused by severe COVID-19 poses great challenges to the public health. However, the underlying pathogenesis of severe cases remains unclear. Here, we find that SARS-CoV-2 infection boosts CD147 inducible up-regulation in the lung tissues of virus-infected rhesus macaques coupled with down-regulated membrane-bound ACE2, which conduces to extended virus infection and severe pathological lesions. Specifically, SARS-CoV-2 infection enhances the expression of transcriptional factor aryl hydrocarbon receptor and facilitates its nucleus translocation, which causes CD147 gene transcription and its up-regulation in protein level, thereby leading to virus susceptibility of the hosts and extended virus infection. Meanwhile, SARS-CoV-2 infection triggers immune imbalance of lung tissues by promoting cell death of CD4 + T cells and B cells and mediating abnormal cell-cell communications, especially for M2 macrophages. Meplazumab, a humanized anti-CD147 antibody, effectively inhibits virus entry and cytokine level, and restores immune balance in the lung tissues of virus-infected rhesus macaque model. Importantly, we further present the cryo-EM structure of CD147-spike complex, and identify five pairs of functional residues for their interaction, which could be interrupted by Meplazumab via steric hindrance effect. Our findings provide direct evidence for CD147-SARS-CoV-2 spike interaction and uncover the pathogenesis of severe COVID-19 caused by CD147-mediated extended virus infection.