Correlation between TGF-β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain-like protease

• Published in: Proteomics (Weinheim) 2012-11, Vol.12 (21), p.3193-3205
• Main Authors: Li, Shih-Wen, Yang, Tsuey-Ching, Wan, Lei, Lin, Ying-Ju, Tsai, Fuu-Jen, Lai, Chien-Chen, Lin, Cheng-Wen
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cell Line; Chi-Square Distribution; Cysteine Endopeptidases - pharmacology; Electrophoresis, Gel, Two-Dimensional; Fundamental and applied biological sciences. Psychology; Host-Pathogen Interactions; Human viral diseases; Humans; Infectious diseases; Leupeptins - pharmacology; Medical sciences; Mice; Microbiology; Miscellaneous; Monocyte-Macrophage Precursor Cells - drug effects; Papain-like protease; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Proteins; Proteome - drug effects; Proteomics - methods; RNA, Messenger - analysis; RNA, Messenger - genetics; SARS coronavirus; TGF-β1; Transforming Growth Factor beta1 - biosynthesis; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Ubiquitin - metabolism; Ubiquitin proteasome; Vimentin; Vimentin - metabolism; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral Proteins - pharmacology
• ISSN: 1615-9853; 1615-9861
• DOI: 10.1002/pmic.201200225

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.