TLR3-dependent upregulation of RIG-I leads to enhanced cytokine production from cells infected with the parainfluenza virus SV5.
Here we address the role of RIG-I and TLR3 in differential cytokine responses against Simian Virus 5 (SV5) and two distinct cytokine inducing SV5 mutants. IFN-beta and IL-6 secretion was induced by infection with P/V-CPI-, an SV5 mutant with P/V substitutions, and were reduced by either siRNA-mediated knockdown of RIG-I expression or by expression of a dsRNA-binding protein. TLR3 overexpression did not alter cytokine secretion induced by P/V-CPI- or by Le-(U5C, A14G), an SV5 promoter mutant. TLR3 signaling by addition of exogenously added dsRNA was not blocked by WT SV5 or either SV5 mutant. Unexpectedly, TLR3 activation in infected cells led to enhanced IL-8 secretion, which correlated with increased RIG-I expression. Dominant negative RIG-I and TRIF supported a model whereby TLR3 activation upregulates RIG-I expression and in turn hypersensitizes cells to RIG-I-mediated cytokine secretion. Implications for crosstalk between different innate immunity pathways in mounting antiviral responses to paramyxoviruses are discussed.
Manuse
Mary J
MJ
Department of Microbiology and Immunology, Wake Forest University, School of Medicine, Winston-Salem, NC 27157-1064, USA.
Parks
Griffith D
GD
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis; D045402:Parainfluenza Virus 5 / Q000276:immunology*; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D015854:Up-Regulation
D033942:Adaptor Proteins, Vesicular Transport; D015850:Interleukin-6; D016209:Interleukin-8; D011971:Receptors, Immunologic; C470409:TICAM1 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases