Although we validated cleavage of several 3Cpro high-confidence candidate substrates identified by TAILS in virus-infected cells, it was not surprising that a few of the top candidate substrates were cleaved in vitro but not during virus infection (e.g., actin, eIF3F, and fascin) (data not shown; see also Table S6 in the supplemental material), indicating that an in vitro cleavage assay approach does not fully recapitulate in vivo infection, as expected. This evidence concerns the gene FSCN1 and viral infectious disease.