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.

Proteomics
|September 1, 2012
PubMed

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.