Antiviral Activity of Oligomerization-Deficient Stat 1

Abstract

Interferon stimulation of cells can activate several hundred target genes, many of which are required for antiviral protection. Promoter binding of tyrosine-phosphorylated (activated) Stat 1 dimers is essentiell for gene induction, a process that often entails the oligomerization of Stat 1 dimers via interactions of their aminoterminal domains. The mutation of a single residue (F 77) in the N-domain of Stat 1 was recently demonstrated to preclude both the dephosphorylation and the oligomerization of Stat 1 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 Stat 1 oligomerization is required for the antiviral activity of interferons. Moreover, the concentration of activated Stat 1 in the nucleus may generally play a critical role for interferon-induced target gene activation.