Correlation of COVID-19 Severity and Immunoglobulin Presence Against Spike and Nucleocapsid Proteins in SARS-CoV-2

Takamatsu, Akane; Oshiro, Satoshi; Mizutani, Naeko; Tada, Tatsuya; Tabe, Yoko; Miida, Takashi; Kirikae, Teruo; Tagashira, Yasuaki

doi:10.1089/vim.2021.0168

Cited by 1 publication

(1 citation statement)

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“…Thus, the SARS-CoV-2 Nucleocapsid protein is more potent at stimulating EndMT, and it seems to play a more crucial role in the course of COVID-19 than the Spike protein. These findings are consistent with previously reported correlations between high concentrations of IgG against the Nucleocapsid protein and poor outcomes in COVID-19 patients [ 64 – 66 ]. Moreover, other studies have shown that TLR4 expression, which, according to the results of our study, is activated mainly by Nucleocapsid, is correlated with severe COVID-19 [ 54 ].…”

Section: Discussionsupporting

confidence: 93%

Diverse roles of SARS-CoV-2 Spike and Nucleocapsid proteins in EndMT stimulation through the TGF-β-MRTF axis inhibited by aspirin

Ciszewski,

Woźniak,

Sobierajska

2024

Cell Commun Signal

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Background The SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular complications associated with inflammation. Acute or prolonged inflammation results in organ fibrosis, the cause of which might be endothelial disorders arising during the endothelial-mesenchymal transition (EndMT). Methods HUVECs and HMEC-1 cells were stimulated with SARS-CoV-2 S (Spike) and N (Nucleocapsid) proteins, and EndMT induction was evaluated by studying specific protein markers via Western blotting. Wound healing and tube formation assays were employed to assess the potential of SARS-CoV-2 to stimulate changes in cell behaviour. MRTF nuclear translocation, ROS generation, TLR4 inhibitors, TGF-β-neutralizing antibodies, and inhibitors of the TGF-β-dependent pathway were used to investigate the role of the TGF-β-MRTF signalling axis in SARS-CoV-2-dependent EndMT stimulation. Results Both viral proteins stimulate myofibroblast trans-differentiation. However, the N protein is more effective at EndMT induction. The TGF-β-MRTF pathway plays a critical role in this process. The N protein preferentially favours action through TGF-β2, whose secretion is induced through TLR4-ROS action. TGF-β2 stimulates MRTF-A and MRTF-B nuclear translocation and strongly regulates EndMT. In contrast, the Spike protein stimulates TGF-β1 secretion as a result of ACE2 downregulation. TGF-β1 induces only MRTF-B, which, in turn, weakly regulates EndMT. Furthermore, aspirin, a common nonsteroidal anti-inflammatory drug, might prevent and reverse SARS-CoV-2-dependent EndMT induction through TGF-β-MRTF pathway deregulation. Conclusion The reported study revealed that SARS-CoV-2 infection induces EndMT. Moreover, it was demonstrated for the first time at the molecular level that the intensity of the EndMT triggered by SARS-CoV-2 infection may vary and depend on the viral protein involved. The N protein acts through TLR4-ROS-TGF-β2-MRTF-A/B, whereas the S protein acts through ACE2-TGF-β1-MRTF-B. Furthermore, we identified aspirin as a potential anti-fibrotic drug for treating patients with SARS-CoV-2 infection.

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Section: Discussionsupporting

confidence: 93%