Correlation between TGF-β1 expression and proteomic profiling induced by severe acute respiratory syndrome
Shih-Wen Li1, Tsuey-Ching Yang, Lei Wan
1Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan; Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan.
Abstract:
Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) papain-like protease (PLpro), a deubiquitinating enzyme, demonstrates inactivation of interferon (IFN) regulatory factor 3 and NF-κB, reduction of IFN induction, and suppression of type I IFN signaling pathway. This study investigates cytokine expression and proteomic change induced by SARS-CoV PLpro in human promonocyte cells. PLpro significantly increased TGF-β1 mRNA expression (greater than fourfold) and protein production (greater than threefold). Proteomic analysis, Western blot, and quantitative real-time PCR assays indicated PLpro upregulating TGF-β1-associated genes: HSP27, protein disulfide isomerase A3 precursor, glial fibrillary acidic protein, vimentin, retinal dehydrogenase 2, and glutathione transferase omega-1. PLpro-activated ubiquitin proteasome pathway via upregulation of ubiquitin-conjugating enzyme E2-25k and proteasome subunit alpha type 5. Proteasome inhibitor MG-132 significantly reduced expression of TGF-β1 and vimentin. PLpro upregulated HSP27, linking with activation of p38 MAPK and ERK1/2 signaling. Treatment with SB203580 and U0126 reduced PLpro-induced expression of TGF-β1, vimentin, and type I collagen. Results point to SARS-CoV PLpro triggering TGF-β1 production via ubiquitin proteasome, p38 MAPK, and ERK1/2-mediated signaling.
Insights
Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro) triggers TGF-β1 production by activating specific cellular pathways. This protease plays a key role in SARS-CoV pathogenesis.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro) is a deubiquitinating enzyme.
- PLpro is known to interfere with host antiviral responses, including interferon (IFN) regulation.
Purpose of the Study:
- To investigate the effects of SARS-CoV PLpro on cytokine expression and proteomic changes in human promonocyte cells.
- To elucidate the signaling pathways involved in PLpro-induced cellular responses.
Main Methods:
- Human promonocyte cells were treated with SARS-CoV PLpro.
- Cytokine expression was analyzed using quantitative real-time PCR and Western blot.
- Proteomic analysis was performed to identify upregulated genes.
- Specific pathway inhibitors (MG-132, SB203580, U0126) were used to investigate signaling mechanisms.
Main Results:
- PLpro significantly increased TGF-β1 mRNA and protein levels.
- PLpro upregulated several TGF-β1-associated genes, including HSP27 and vimentin.
- PLpro activated the ubiquitin proteasome pathway and signaling pathways involving p38 MAPK and ERK1/2.
- Inhibition of the proteasome or MAPK pathways reduced PLpro-induced TGF-β1 and vimentin expression.
Conclusions:
- SARS-CoV PLpro induces TGF-β1 production through the ubiquitin proteasome, p38 MAPK, and ERK1/2 signaling pathways.
- These findings highlight a novel mechanism by which SARS-CoV PLpro modulates the host immune response and cellular processes.
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