title: Induction of STAT1 phosphorylation at serine 727 and expression of proinflammatory cytokines by porcine reproductive and respiratory syndrome virus.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a viral pathogen that causes acute respiratory illnesses in young pigs. Since 1987, PRRSV has contributed substantial economic losses to the swine industry. Elevation of proinflammatory cytokines in PRRSV-infected pigs is thought to contribute to PRRSV pathogenesis. In this study, PRRSV VR-2385, a Type 2 strain with moderate virulence, was found to induce phosphorylation of signal transducer and activator of transcription 1 (STAT1) at serine 727 (pSTAT1-S727) in MARC-145 cells. No phosphorylated STAT1 at tyrosine 701 was detected, which indicates that the pSTAT1-S727 elevation was interferon-independent. The PRRSV-induced pSTAT1-S727, however, was dose-dependent and its levels increased with infection time. IngelVac PRRS MLV strain had a minimal effect on pSTAT1-S727. Compared to MLV-infected cells, VR-2385 infection caused significantly higher level of expression of proinflammatory cytokines, including interleukin 1 beta (IL-1beta) and IL-8. The VR-2385-induced pSTAT1-S727 and cytokine expression were reduced after SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), or methylthioadenosine (MTA), a methyl transferase inhibitor, was added to the cells. The SB203580 and MTA-mediated inhibition suggested that the virus-induced pSTAT1-S727 was dependent on p38 MAPK pathway. In primary porcine alveolar macrophages (PAMs), VR-2385 also induced pSTAT1-S727 and expression of proinflammatory cytokines and chemokines, including IL-1beta, IL-8, chemokine ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 10 (CXCL10). Similarly, SB203580 treatment of PAM cells blocked the elevation of pSTAT1-S727 and cytokine expression. Overexpression of individual viral proteins showed that non-structural protein 12 (nsp12) was able to induce elevation of pSTAT1-S727 and the expression of IL-1β and IL-8. These results indicated that PRRSV VR-2385 induces pSTAT1-S727 and the expression of proinflammatory cytokines, which contributes to the insight of PRRSV pathogenesis.
authors: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
authors: Ying
authors: Y
authors: Yu
authors: Rong
authors: R
authors: Wang
authors: Yuchen
authors: Y
authors: Nan
authors: Linsheng
authors: L
authors: Zhang
authors: Yanjin
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000378:metabolism*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D014764:Viral Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D050794:STAT1 Transcription Factor; D014764:Viral Proteins; D012694:Serine; D008780:Methyltransferases; D048051:p38 Mitogen-Activated Protein Kinases
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