Antiviral Activity of Oligomerization-Deficient Statl

摘要

Interferon stimulation of cells can activate several hundred target genes, many of which are required for antiviral protection. Promoter binding of tyrosine-phosphorylated (activated) Statl dimers is essentiell for gene induction, a process that often entails the oligomerization of Statl dimers via interactions of their aminoterminal domains. The mutation of a single residue (F77) in the N-domain of Statl was recently demonstrated to preclude both the dephosphorylation and the oligomerization of Statl dimers. Here, we investigated the influence of defective oligomerization on a complex phenotype such as the induction of an antiviral state. It was found that the antiviral protection conferred by interferon-a was strongly reduced, whereas the interferon-g response was not measurably affected. These results indicate that Statl oligomerization is required for the antiviral activity of interferons. Moreover, the concentration of activated Statl in the nucleus may generally play a critical role for interferon-induced target gene activation.