The S1 spike protein of SARS-CoV-2 upregulates the ERK/MAPK signaling pathway in DC-SIGN-expressing THP-1 cells.

Publication date: Mar 05, 2024

Dendritic cells, macrophages, neutophils and other antigen-presenting cells express various C-type lectin receptors that function to recognize the glycans associated with pathogens. DC-SIGN (the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) binds various pathogens such as HIV gp120, the Ebola glycoprotein, Hemagglutinin, and the dengue virus glycoprotein in addition to the SARS-CoV-2 Spike protein, and also triggers antigen presenting cell endocytosis and immune escape from systemic infections. Many studies on the binding of SARS-CoV-2 spike protein with glycans have been published but the underlying mechanism by which intracellular signaling occurs remains unclear. In this study, we report that the S1 spike protein of SARS-CoV-2 induces the phosphorylation of ERKs in THP-1 cells, a DC-SIGN-expressing human monocytic leukemic cell line. On the other hand, the phosphorylation level of NF-_705B remained unchanged under the same conditions. These data suggest that the major cell signaling pathway regulated by S1 spike protein is the ERK pathway, which is superior to the NF-_705B pathway in these DC-SIGN-expressing THP-1 cells and may contribute to immune hyperactivation in SARS-CoV-2 infections. Additionally, several glycans such as mannans, mannosylated BSA, the serum amyloid beta protein, and ICAM3 suppressed ERK phosphorylation suggesting that these molecules are target molecules for SARS-CoV-2 infection by suppressing immune hyperactivation that occurs in the ERK signaling pathway.

Concepts Keywords
Amyloid DC-SIGN
Hiv Dendritic cell
Neutophils ERK
Serum NF-κB
Target SARS-CoV-2 S1


Type Source Name
pathway KEGG MAPK signaling pathway
disease IDO cell
disease VO Glycoprotein
disease VO Dengue virus
pathway KEGG Endocytosis
disease MESH infections
disease VO report
disease MESH SARS-CoV-2 infections
pathway REACTOME SARS-CoV-2 Infection

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