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J Virol, February 1998, p. 1616-1622, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Analysis of Ground Squirrel Hepatitis Virus Enhancer II

Geneviève Fourel,1,dagger François Ringeisen,2 Marc Flajolet,1 Pierre Tiollais,1 and Marie Annick Buendia1,*

Unité de Recombinaison et Expression Génétique, INSERM U163,1 and Unité des Virus Oncogènes, CNRS URA1644,2 Institut Pasteur, 75724 Paris Cedex 15, France

Received 2 July 1997/Accepted 15 October 1997

We have characterized a major regulatory element of ground squirrel hepatitis virus (GSHV) located within a 90-nucleotide fragment of the core promoter upstream sequences and have compared its organization to that of woodchuck hepatitis virus (WHV) enhancer II (We2). The GSHV element (Ge2) stimulates transcription from the viral core promoter and heterologous promoters in an orientation-independent manner but displays a lower level of activity than We2 in transient transfection assays in human hepatoma cells. The general organization of Ge2 into binding sites for the liver-enriched HNF-1 and HNF-4 proteins and for ubiquitous factors of the NF1 and Oct families was found to be mostly conserved with respect to the homologous We2 region. Accordingly, transactivation by HNF-1 and HNF-4 plays an essential role in the liver-specific transcriptional activity of both the GSHV and WHV core promoters. Distinctive features of the GSHV enhancer consist of its ability to bind C/EBP family factors in a central motif that overlaps with one of the two HNF-4 sites and its differential binding affinities for HNF-4.

* Corresponding author. Mailing address: Unité de Recombinaison et Expression Génétique, Département des Rétrovirus, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33/1 45 68 88 66. Fax: 33/1 45 68 89 43. E-mail: mbuendia{at}pasteur.fr.

dagger Present address: Ecole Normale Supérieure de Lyon, CNRS UMR49, Lyon, France.






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