title: North American porcine reproductive and respiratory syndrome viruses inhibit type I interferon production by plasmacytoid dendritic cells.
abstract: Although enveloped viruses typically trigger the prodigious secretion of alpha interferon (IFN-α) by plasmacytoid dendritic cells (pDC), porcine pDC remain quiescent when exposed to porcine reproductive and respiratory syndrome virus (PRRSV). This inactivity is likely due to virus-mediated interference since the typical IFN-α response by either purified or nonsorted porcine pDC to transmissible gastroenteritis virus (TGEV) or the Toll-like receptor 9 agonist, oligodeoxynucleotide (ODN) D19, was markedly reduced in the presence of PRRSV. Suppression occurred independently of virus viability and acidification of pDC early endosomes but correlated with diminished levels of IFN-α mRNA. This change was attributed to an abrogation of transcription resulting from a decrease in the otherwise enhanced amounts of the requisite interferon regulatory factor 7 (IRF-7), whose gene expression in turn was limited as a consequence of a lessened availability of nuclear-localized signal transducer and activator of transcription 1 (STAT1). While PRRSV also inhibited tumor necrosis factor alpha (TNF-α) synthesis by pDC responding to either agent, only the interleukin-2 (IL-2) and IL-6 production instigated by ODN D19 exposure was blocked. Likewise, PRRSV did not impact a specific TGEV-associated enhancement of IL-8 expression. Moreover, an augmented phosphorylation of NF-κB seen in activated pDC was not only unaffected by PRRSV but actually occurred in its presence. Thus, as supported by a demonstrated resilience of pDC to PRRSV infection, this pathogen may interact with a cell surface protein(s) to selectively impede the completion of cascades involved in cytokine production by stimulated pDC.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calzada-Nova
authors.forename: William M
authors.initials: WM
authors.lastname: Schnitzlein
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Husmann
authors.forename: Federico A
authors.initials: FA
authors.lastname: Zuckermann
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015536:Down-Regulation; D015870:Gene Expression; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D009656:North America; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000276:immunology
chemical_list: D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger