title: Porcine reproductive and respiratory syndrome virus (PRRSV) infection activates chemokine RANTES in MARC-145 cells.
abstract: RANTES (regulated upon activation, normally T-cell expressed and presumably secreted), a CC chemokine, plays an important role in the inflammatory response associated with viral infections. Previous studies have demonstrated that infection with porcine reproductive and respiratory syndrome virus (PRRSV) induces RANTES transcription in vitro and in vivo. However, the molecular mechanism remains unclear. In this study, real-time RT-PCR and promoter luciferase reporter assays showed that PRRSV infection significantly upregulates RANTES gene transcription in both a time- and dose-dependent manner and this induction requires viral replication in MARC-145 cells. Promoter mutagenesis experiments found that the nuclear factor (NF-κB) binding sites play an important role in PRRSV-induced RANTES transcription, while the interferon-stimulated responsive element (ISRE) site is not essential. PRRSV-induced RANTES transcription was dramatically inhibited by administration of a dominant-negative mutant of IκB kinase alpha (mIκBα), NF-κB inhibitor BAY11-7082 or ERK1/2 inhibitor U0126. In addition, the use of dominant-negative mutants of various adaptor molecules of the Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling pathways demonstrated that PRRSV upregulated RANTES transcription is dependent on myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing IFN-β (TRIF) and TNF receptor-associated factor 6 (TRAF6), indicating that the TLR signaling pathway is involved in PRRSV-induced RANTES activation.
authors.affiliation: Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.forename: Dang
authors.initials: D
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D019318:Porcine Reproductive and Respiratory Syndrome / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine / Q000276:immunology* / Q000821:virology*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018946:Chemokine CCL5; D053594:Myeloid Differentiation Factor 88; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; D020928:Mitogen-Activated Protein Kinases