INFLUENZA-VIRUS NS1 PROTEIN ALTERS THE SUBNUCLEAR LOCALIZATION OF CELLULAR SPLICING COMPONENTS

Intranuclear structure was studied in influenza virus-infected cells by immunofluorescence microscopy with antibodies specific for fibrillarin, the splicing factor SC35 and the autoantigen p80 coilin. In the course of the infection, an increase in the number of coiled bodies was observed, with a parallel decrease in their size. In addition, the normal speckled pattern of the SC35 factor was altered to generate a more punctate distribution. However, no alteration was observed in the fibrillarin staining pattern. Since an alteration in the splicing of both viral and cellular mRNAs upon expression of influenza virus NS1 protein has been reported previously, the possible effects of NS1 expression on intranuclear structure were assayed. The increase in the coiled body numbers was not specific for the expression of NS1 protein, but alterations in the nuclear location of small ribonucleoprotein particles, as determined by immunofluorescence with an anti-Sm serum or the SC35 splicing factor, were produced by the sole expression of NS1 protein. These results correlate with the previously reported inhibition of splicing induced by NS1 protein expression and suggest an interaction of this influenza virus protein with the cellular splicing machinery.