title: Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells.
abstract: Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infections are characterized by prolonged viremia and viral shedding consistent with incomplete immunity. Type I interferons (IFN) are essential for mounting efficient antiviral innate and adaptive immune responses, but in a recent study, North American PRRSV genotype 2 isolates did not induce, or even strongly inhibited, IFN-α in plasmacytoid dendritic cells (pDC), representing "professional IFN-α-producing cells". Since inhibition of IFN-α expression might initiate PRRSV pathogenesis, we further characterized PRRSV effects and host modifying factors on IFN-α responses of pDC. Surprisingly, a variety of type 1 and type 2 PRRSV directly stimulated IFN-α secretion by pDC. The effect did not require live virus and was mediated through the TLR7 pathway. Furthermore, both IFN-γ and IL-4 significantly enhanced the pDC production of IFN-α in response to PRRSV exposure. PRRSV inhibition of IFN-α responses from enriched pDC stimulated by CpG oligodeoxynucleotides was weak or absent. VR-2332, the prototype genotype 2 PRRSV, only suppressed the responses by 34%, and the highest level of suppression (51%) was induced by a Chinese highly pathogenic PRRSV isolate. Taken together, these findings demonstrate that pDC respond to PRRSV and suggest that suppressive activities on pDC, if any, are moderate and strain-dependent. Thus, pDC may be a source of systemic IFN-α responses reported in PRRSV-infected animals, further contributing to the puzzling immunopathogenesis of PRRS.
authors.affiliation: Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, Mittelhäusern, 3147, Switzerland. artur.summerfield@ivi.admin.ch.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Baumann
authors.forename: Enric
authors.initials: E
authors.lastname: Mateu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murtaugh
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005434:Flow Cytometry / Q000662:veterinary; D005838:Genotype; D016898:Interferon-alpha / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014774:Virulence
chemical_list: D016898:Interferon-alpha