In addition to STAT1, we show that hPIV3-C interacts directly with GRB2 and enhances MAPK/ERK signaling downstream of EGF receptor (EGFR). Our data give the first example of a Paramyxoviridae protein that contributes to the stimulation of EGFR and MAPK/ERK pathway and provides molecular basis to this activity. This pathway has been known for decades as a prime target of DNA tumor viruses and oncogenic retroviruses, and its activation represents an essential step toward carcinogenesis [3, 42] . But recent data demonstrate that non-oncogenic RNA viruses also activate this signaling cascade to support viral replication and spreading [31] . Whether it is activated upon EGFR engagement or other means, MAPK/ERK pathway regulates a multiplicity of cellular processes including proliferation, differentiation, development, cell survival and inflammation. As a consequence, how the activation of MAPK/ERK pathway promotes viral replication is a complex question. Interestingly, two non-oncogenic RNA viruses associated with acute respiratory tract infections have been recently reported to modulate the EGFR pathway. Both human respiratory syncytial virus (hRSV), a member of Paramyxoviridae like hPIV3, and a rhinovirus that belongs to Picornaviridae family activate EGFR and MAPK/ERK pathway [25, 27] . Infection of epithelial cells by these viruses stimulates the processing and activation of EGFR ligands by membrane matrix metalloproteinase and subsequent engagement of EGFR through autocrine/paracrine mechanisms. Experiments performed on rhinovirus show that viral replication and TLR3 engagement by viral RNA are both required to activate the EGFR and MAPK/ERK pathway [27] . In this report, we show that hPIV3 infection also activates MAPK/ERK pathway in the absence of external stimuli, a phenomenon that possibly relies on the engagement of pathogen recognition receptors. Although hPIV3-C alone is unable to activate this pathway, our data suggest that expression of this virulence factor enhances MAPK/ERK activation above normal level in infected cells, thereby contributing to viral replication and pathogenesis.