title: Porcine reproductive and respiratory syndrome virus activates the transcription of interferon alpha/beta (IFN-α/β) in monocyte-derived dendritic cells (Mo-DC).
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be a poor inducer of interferon alpha/beta (IFN-α/β), which may contribute to the delayed development of adaptive immunity and the resultant viral persistence. However, the exact mechanism by which PRRSV inhibits the induction of IFN-α/β during infection of its natural host cells remains less well defined. Here, we show that PRRSV efficiently activates the transcription of IFN-α/β in porcine monocyte-derived dendritic cells (Mo-DC) in a time-dependent and transient manner; and this effect is dependent on the activation of phosphatidylinositol 3-kinase (PI3K). Despite the abundant IFN-α transcripts detected in PRRSV-infected Mo-DC, little or no detectable IFN-α is found in the supernatants and cell lysates of PRRSV-infected Mo-DC, suggesting that PRRSV either blocks the translation of IFN-α or inhibits the RNA processing and transport. Furthermore, we observed that PRRSV infection significantly reduced the induction of IFN-α by Poly I:C treatment; and virus replication is essential to the effect since heat-inactivated PRRSV has no effect on IFN-α induction by Poly I:C. Overall, our data provide evidence for the possible role of PI3K in the activation of the transcription of IFN-α/β by PRRSV. We conclude that PRRSV inhibits the induction of IFN-α in Mo-DC by as yet undefined post-transcriptional mechanisms.
authors.affiliation: Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Hanmo
authors.initials: H
authors.lastname: Zhang
authors.forename: Xueshui
authors.initials: X
authors.lastname: Guo
authors.forename: Eric
authors.initials: E
authors.lastname: Nelson
authors.forename: Jane
authors.initials: J
authors.lastname: Christopher-Hennings
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism; D019316:Porcine respiratory and reproductive syndrome virus; D012323:RNA Processing, Post-Transcriptional; D013552:Swine; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta; D019869:Phosphatidylinositol 3-Kinases; D011070:Poly I-C