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Curr Genet

Title:		Expression of functional HIV-1 integrase in the yeast Saccharomyces cerevisiae leads to the emergence of a lethal phenotype: potential use for inhibitor screening
Author(s):		Caumont AB; Jamieson GA; Pichuantes S; Nguyen AT; Litvak S; Dupont C;
Address:		"IBGC-CNRS, Laboratoire de Replication et Expression des Genomes Eucaryotes et Retroviraux, 1 rue Camille St Saens, F-33077 Bordeaux-Cedex, France"
Journal Title:		Curr Genet
Year:		1996
Volume:		29
Issue:		6
Page Number:		503 - 510
DOI:		10.1007/BF02426953
ISSN/ISBN:		0172-8083 (Print) 0172-8083 (Linking)
Abstract:		"The integrase of the human immunodeficiency virus type 1 (HIV-1) has been expressed in yeast in order to investigate its potential lethal effect mediated by DNA damage. To this end, we have constructed an expression plasmid containing the retroviral integrase gene under the control of the inducible promotor ADH2/GAPDH which is regulated by the glucose concentration of the medium. Haploid yeast strain W303-1A did not appear to be clearly sensitive to HIV-1 integrase expression. However, disruption of the RAD 52 gene, which is involved in the repair of double-strand DNA breaks, strongly increased the deleterious effects of the retroviral enzyme in this yeast strain. The diploid strain constructed with W303-1A and an isogenic strain of the opposite mating type also showed a strong sensitivity to the HIV-1 integrase. Under yeast culture conditions allowing moderate integrase synthesis, the deleterious effect was totally abolished by missense integrase mutations, which are known to abolish HIV-1 integrase activities in vitro. We conclude that the lethal phenotype due to HIV-1 integrase expression in yeast may be closely related to the HIV-1 integration reaction in infected human cells, and that yeast may be a useful tool to study the HIV-1 integration process and to screen drugs capable of inhibiting HIV-1 integration in vivo"
Keywords:		"Antiviral Agents/pharmacology Base Sequence Binding Sites/genetics DNA Damage DNA Nucleotidyltransferases/biosynthesis/*genetics DNA Primers/genetics Drug Evaluation, Preclinical/methods Gene Expression Genes, Viral HIV-1/*enzymology/*genetics Humans Inte;"
Notes:		"MedlineCaumont, A B Jamieson, G A Pichuantes, S Nguyen, A T Litvak, S Dupont, C eng Research Support, Non-U.S. Gov't 1996/05/01 Curr Genet. 1996 May; 29(6):503-10. doi: 10.1007/BF02426953"