Induction of MAPK/ERK pathway by RNA viruses has numerous consequences on cell biology. First, it results in increased expression of inflammatory factors, in particular cytokines and chemokines that recruit cellular effectors of immunity [27, [43] [44] [45] [46] [47] . MAPK/ERK pathway was also reported to block the antiviral response induced by IFN-a/b, making its activation beneficial to virus replication [29] . Another consequence of MAPK/ERK pathway activation is the induction of mucin production by infected epithelial cells [24, 27] . Although mucin expression is a critical innate defense system, excessive production of mucus results in the obstruction of airways and delays the elimination of pathogens. Finally, it has been demonstrated in vitro that upon hRSV infection, activation of EGFR and MAPK/ERK pathway sustains viral replication by retarding the death of infected cells [25] . Altogether, these data suggest that although a moderate activation of MAPK/ERK pathway contributes to the innate response against viruses, an excessive activation leads to deleterious inflammation, inhibition of IFN-a/b response, airway obstruction and infected cell survival Figure 6 . Identification of a minimal hPIV3-C region interacting with GRB2. Fragments of hPIV3-C were generated and tested for their ability to interact with GRB2 following the procedure described in Figure 5A . (A) The first iteration identified a GRB2 binding region of 124 AA. After two (B), three (C) and four additional rounds (D), this domain was finally reduced to a minimal GRB2 binding motif of 99 AA. This binding domain, encompassing position 97 to 195, is contained in the STAT1 binding region of hPIV3-C previously identified in Figure 5 . doi:10.1371/journal.ppat.1000587.g006 hPIV3-C Impact on IFN-a/b and EGF Pathways [28] . Therefore, it is tempting to speculate that hPIV3-C interaction with GRB2 and EGFR pathway participates in such deregulation of airway epithelium homeostasis to promote hPIV3 replication and spreading. A consequence of such perturbations could be an aggravation of chronic inflammatory airway diseases like asthma or chronic obstructive pulmonary disease as already suggested by epidemiological links with Paramyxoviridae infections and in vivo models [48, 49] .