Identification of the NF-κB-related proteins recruited during EGFP tagged HSV-1 replication in THP-1 cells: contribution of miRNA 146a as regulatory key in NF-κB activation

The transcriptional factor NF-κB appears to be an attractive target for common human viral pathogens and it plays an important role in regulating innate and adaptive immunity, cell proliferation and survival, promoting inflammation and tumors development. Here we have demonstrated a canonical activation of the transcription factors κB in THP-1 cells upon HSV-1 replication. By using a recombinant tagged HSV-1/EGFP virus, we reported the capability of the virus to activate the nuclear transcription factor κB at single cell level. In addition, we show that the upregulation of the pro-inflammatory miRNA-146a during viral replication is strictly dependent on NF-κB activation. Indeed, DN IκBα THP-1 cells, ectopically expressing a dominant negative mIkBα, did not show the recruitment of miR-146a following HSV-1 infection. It is already know, that transcription factors κB can target and regulate the expression of specific miRNAs and, vice versa, miRNAs can target NF-κB. Our data demonstrate that HSV-1 is able to modulate expression of miR-146a in a NF-κB pathway-dependent manner in order to regulate transcriptional gene expression of the well-known miR146a targets such as the interleukin-1 receptor-associated kinase 1 (IRAK-1). These data suggest that expression of NF-κB-sensitive miRNA-146a induced by HSV-1 modulate NF-kB activation trough targeting adaptor protein IRAK1 during HSV-1 replication.