Porcine reproductive and respiratory syndrome virus suppresses post-transcriptionally the protein expression of IFN-β by upregulating cellular microRNAs in porcine alveolar macrophages in vitro
- Lilin Wang
- Lei Zhou
- Dongmei Hu
- Xinna Ge
- Xin Guo
- Hanchun Yang
Published online on: October 30, 2017
Copyright: © Wang et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to inhibit the response of type I interferon (IFN) both in vivo and in vitro. However, the post‑transcriptional mechanism by which PRRSV suppresses type Ⅰ IFN induction in virus-infected host cells remains unclear. The present study first demonstrated that PRRSV inhibited post-transcriptionally the protein induction of IFN-β in primary porcine alveolar macrophages (PAMs) during early infection, and the inhibition effect mediated by the Chinese highly pathogenic (HP)-PRRSV was stronger. Next, we analyzed the cellular microRNA (miRNA)-modulated protein expression of porcine IFN-β by dual firefly/Renilla luciferase reporter assay, transfection of miRNA mimics and inhibitor assay and polyinosinic-polycytidylic acid (poly I:C) treatment of PAMs, showing that porcine miRNAs including let-7b, miR‑26a, miR-34a and miR-145 are able to inhibit IFN-β protein expression in primary PAMs by directly targeting sequences within the porcine IFN-β 3'UTR locating at 160-181, 9-31, 27-47 and 12-32 bp, respectively. Finally, we confirmed that let-7b, miR-26a, miR-34a and miR-145, were upregulated in PRRSV‑infected PAMs early in vitro, and the expression level of these miRNAs in HP-PRRSV JXwn06‑infected PAMs were higher than those in low pathogenic PRRSV HB-1/3.9-infected PAMs. The endogenous cellular miRNA-mediated inhibition of IFN-β induction in PRRSV‑infected PAMs early could be relieved by miRNA antagonists. Taken together, our findings suggest for the first time that PRRSV can suppress post-transcriptionally protein expression of IFN-β by upregulating cellular miRNAs in PAMs in vitro, providing novel insight into mechanisms in relation to the PRRSV-mediated immunomodulation of porcine innate immunity.