Abstract: The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian

origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk

(Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL).

This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol

3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1

can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which

results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed

using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a

physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize

the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host

cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif.