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SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2
Nima Taefehshokr1, Alex Lac1, Angela M Vrieze1
1Department of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Journal of Cell Science
|April 29, 2024
Summary
The SARS-CoV-2 main protease, NSP5, suppresses Major Histocompatibility Complex (MHC) II expression by delivering HDAC2 to the CIITA promoter, hindering the adaptive immune response.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- SARS-CoV-2 infection impairs antigen presentation by downregulating MHC II on antigen-presenting cells.
- The precise molecular mechanism behind SARS-CoV-2-induced MHC II downregulation remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which SARS-CoV-2 downregulates Major Histocompatibility Complex (MHC) II expression.
- To identify the viral protein responsible for suppressing MHC II and its mode of action.
Main Methods:
- Analysis of protein and gene expression in human antigen-presenting cells.
- Investigated the role of SARS-CoV-2 main protease (NSP5) in MHC II regulation.
- Assessed the impact of HDAC2 and IRF3 on the CIITA promoter.
Main Results:
- SARS-CoV-2 main protease (NSP5) downregulates MHC II expression by reducing CIITA levels.
- NSP5 delivers HDAC2 to the CIITA promoter, leading to deacetylation and inactivation of the promoter, independent of NSP5's protease activity.
- Suppression of MHC II was reversed by CIITA re-expression or HDAC2 knockdown.
Conclusions:
- Identified a novel mechanism where SARS-CoV-2 NSP5 inhibits MHC II expression through HDAC2-mediated CIITA promoter inactivation.
- This viral strategy likely weakens the adaptive immune response by impairing antigen presentation.
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