THE EXPRESSION OF THE ESSENTIAL NUCLEAR SPLICING FACTOR SC35 IS ALTERED BY HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

In order to identify cellular genes differentially expressed during hu man immunodeficiency virus 1 (HIV-1) infection, we conducted a screen using differential display. The sequence of one of the clones, 0085, w as identical to a sequence present in the RNA splicing factor SC35. Si nce splicing is an essential point of control during HIV gene expressi on, we carried out additional experiments to examine SC35 expression d uring HIV infection. RNA blots confirmed that SC35 RNA was induced fol lowing HIV infection; a 2-3-fold increase in expression of SC35 RNA wa s detected by day 2 of HIV infection. Fluorescence-activated cell-sort ing revealed concomitant increases in SC35 protein and double staining studies demonstrated that increases in SC35 protein occurred specific ally in the HIV-infected cells. Laser scanning confocal microscopy rev ealed SC35 was associated with 2 mu m 'nuclear speckles' in both infec ted and uninfected cells, suggesting that increases in SC35 accumulate d in these nuclear structures and that HIV infection did not alter the intracellular distribution of SC35. These findings indicate that an e ssential splicing factor is induced after HN infection, suggesting tha t the consequences of HIV infection include alterations in relative le vels of a splicing factor. (C) 1998 Elsevier Science B.V. All rights r eserved.