MicroRNA-30c is utilized by PRRSV in immune evasion through targeting JAK1 in the type I interferon signaling pathway (VIR5P.1153)
2015; American Association of Immunologists; Volume: 194; Issue: 1_Supplement Linguagem: Inglês
10.4049/jimmunol.194.supp.148.21
ISSN1550-6606
AutoresQiong Zhang, Chen Huang, Qian Yang, Li Gao, Hsiao‐Ching Liu, Jun Tang, Wen-hai Feng,
Tópico(s)Viral gastroenteritis research and epidemiology
ResumoAbstract Innate immune responses constitute the first line of defense against viral infections, and many viruses are capable of interfering with IFN signaling to escape from the innate immune responses and facilitate their proliferation and spread. Here, we found that a host miRNA, miR-30c, was up-regulated by porcine reproductive and respiratory syndrome virus (PRRSV) via activating NF-κB and benefited its infection. Subsequently, we demonstrated that miR-30c impaired the type I interferon (IFN-I) signaling pathway by targeting JAK1, resulting in the enhancement of PRRSV infection. To our knowledge, this is the first report of a host miRNA that suppresses IFN-I signaling by targeting JAK1, a vital component in the signaling of IFN-I. In addition, we found that miR-30c targeting sequences in JAK1 were conserved throughout mammals, and miR-30c was able to enhance both DNA virus (Herpes simplex virus) and negative-strand RNA virus (influenza virus) replications. Moreover, miR-30c is induced by IFN-I and acts as a negative feed-back modulator. These broad spectrum results suggest that miR-30c sets host IFN-I signaling response a threshold and is a universal regulator of viral replication. Our findings thus improve our understanding of the pathogenesis of PRRSV infection by identifying a new strategy whereby PRRSV to escape IFN-I-mediated antiviral immune responses by engaging miR-30c.
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