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SARS-CoV-2 Accessory Protein ORF8 Targets the Dimeric IgA Receptor pIgR.
- Source :
-
Viruses [Viruses] 2024 Jun 22; Vol. 16 (7). Date of Electronic Publication: 2024 Jun 22. - Publication Year :
- 2024
-
Abstract
- SARS-CoV-2 is a highly pathogenic respiratory virus that successfully initiates and establishes its infection at the respiratory mucosa. However, little is known about how SARS-CoV-2 antagonizes the host's mucosal immunity. Recent findings have shown a marked reduction in the expression of the polymeric Ig receptor (pIgR) in COVID-19 patients. This receptor maintains mucosal homeostasis by transporting the dimeric IgA (dIgA) and pentameric IgM (pIgM) across mucosal epithelial cells to neutralize the invading respiratory pathogens. By studying the interaction between pIgR and SARS-CoV-2 proteins, we discovered that the viral accessory protein Open Reading Frame 8 (ORF8) potently downregulates pIgR expression and that this downregulation activity of ORF8 correlates with its ability to interact with pIgR. Importantly, the ORF8-mediated downregulation of pIgR diminishes the binding of dIgA or pIgM, and the ORF8 proteins of the variants of concern of SARS-CoV-2 preserve the function of downregulating pIgR, indicating the importance of this conserved activity of ORF8 in SARS-CoV-2 pathogenesis. We further observed that the secreted ORF8 binds to cell surface pIgR, but that this interaction does not trigger the cellular internalization of ORF8, which requires the binding of dIgA to pIgR. These findings suggest the role of ORF8 in SARS-CoV-2 mucosal immune evasion.
- Subjects :
- Humans
Immunoglobulin A immunology
Viral Proteins genetics
Viral Proteins metabolism
Viral Proteins immunology
Down-Regulation
Immunity, Mucosal
HEK293 Cells
Immune Evasion
Animals
Receptors, Fc
Receptors, Polymeric Immunoglobulin genetics
Receptors, Polymeric Immunoglobulin metabolism
SARS-CoV-2 immunology
SARS-CoV-2 genetics
COVID-19 immunology
COVID-19 virology
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 39066171
- Full Text :
- https://doi.org/10.3390/v16071008