To identify cellular targets of hPIV3-C, this viral protein was used as bait in the yeast two-hybrid system to screen a human cDNA library. The screen was performed at saturation with a 10-fold coverage of the library (50.10 +6 diploids), and positive yeast colonies growing on selective medium were analyzed by PCR and sequencing to identify binding partners of hPIV3-C. STAT1 and GRB2 were the main interactors of hPIV3-C identified in the screen with 5 and 150 yeast colonies corresponding to these cellular proteins, respectively. In both cases, cDNA clones retrieved from the screen corresponded to full-length STAT1 and GRB2 in frame with the Gal4-AD transactivation domain. To validate these interactions in human cells, GST-tagged hPIV3-C was expressed in HEK-293T cells and purified with glutathion-sepharose beads. As shown in Figure 1B and 1C, endogenous STAT1 and GRB2 co-purified with hPIV3-C. Highly divergent C proteins from measles virus (MV-C) and Nipah virus (Nipah-C) failed to do so, thereby demonstrating the specificity of identified interactions. Binding to STAT1 provides molecular basis to the inhibition of IFN-a/b signaling by hPIV3-C [18] , and parallels the interaction previously identified between Sendai virus C protein and mouse STAT1 [15] . Altogether, this suggests that STAT1 is a specific cellular interactor of Respirovirus C proteins. In contrast, binding to GRB2 is unexpected and suggests a new function for hPIV3-C that we decided to investigate.