In an attempt to answer this question, we performed a yeast two-hybrid screen and we report here the identification of STAT1 and GRB2 as direct interactors of hPIV3-C. Although binding to STAT1 accounts for hPIV3-C ability to block IFN-a/b signaling, the interaction with GRB2 was unexpected. This adaptor protein bridges growth factor receptor tyrosine kinases (RTKs), like Epidermal Growth Factor (EGF) receptor, to the mitogenactivated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Upon engagement by their ligands, RTKs autophosphorylate on tyrosine residues to recruit adaptor proteins containing phosphotyrosine binding (PTB) or Src homology 2 (SH2) domains like GRB2 [21] . Once associated to RTKs by its SH2 domain, GRB2 recruits the guanine nucleotidereleasing factor son-of-sevenless (SOS) to activate Ras. Downstream events include MAPK/ERK kinase (MEK1/2) activation, which in turn phosphorylates ERK1/2. Finally, phosphorylated ERK1/2 directly or indirectly activates numerous cellular targets including transcription factors (e.g. Elk1, SAP1, SAP2, c-Fos, CREB, SRF) but also cellular factors that control mRNA translation like eukaryotic initiation factor 4E (eIF4E) or small ribosomal subunit S6 protein [22, 23] . Growth factor binding to RTKs regulates a multiplicity of cellular processes including proliferation, differentiation and survival. In the respiratory tract, this signaling cascade has been shown to trigger inflammation and mucus secretion by epithelial cells [24] [25] [26] [27] , suggesting a critical role in innate immunity [28] . However, excessive activation of this pathway could benefit to virus replication by inhibiting IFN-a/b signaling [29] and promoting infected cell survival [25] . Altogether, these data provided a rational to investigate the functional impact of hPIV3-C expression on IFN-a/b vs EGF receptor and MAPK/ERK signaling pathways.