Porcine reproductive and respiratory syndrome virus (PRRSV) infection activates chemokine RANTES in MARC-145 cells.

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.

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