Inactivation of the SNF5 transcription factor gene abolishes the lethal phenotype induced by the expression of HIV-1 integrase in yeast

The ubiquitous human transcription factor Inil has been shown to interact w ith HIV-1 integrase (IN) and to stimulate in vitro the reactions catalyzed by this enzyme. We have previously used a yeast model to study the effect o f HIV-1 IN expression (Caumont, A.B., Jamieson; G.A., Pichuantes, S., Nguye n, A.T., Litvak, S., Dupont, C.-H., 1996. Expression of functional HIV-1 in tegrase in the yeast Saccharomyces cerevisiae leads to the emergence of a l ethal phenotype: potential use for inhibitor screening. Curr. Genet. 29, 50 3-510). Here, we describe the effect of the inactivation of the gene encodi ng for SNF5, a yeast transcription factor homologous to Inil, on the lethal ity induced by the expression of HIV-1 IN in yeast. We observed that the re troviral IN was unable to perform its lethal activity in cells where the SN F5 gene has been disrupted, suggesting that SNF5 may play a role in the let hal effect induced by IN in yeast. SNF5 inactivation affects neither yeast viability nor expression of HIV-1 IN. Given the homology between SNF5 and i ts human counterpart Inil, our results suggest that this factor may be impo rtant for IN activity in infected cells. Moreover, given the important role proposed for this transcription factor in the integration step and the fac t that it is dispensable for cell viability, the interaction between Inil/y SNF5 and HIV-1 IN should become a potential target in the search for new an tiretroviral agents. (C) 2000 Elsevier Science B.V. All rights reserved.