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J Virol, July 1998, p. 5526-5534, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

An Interferon Regulatory Factor Binding Site in the U5 Region of the Bovine Leukemia Virus Long Terminal Repeat Stimulates Tax-Independent Gene Expression

Véronique Kiermer,1,* Carine Van Lint,1,2 Delphine Briclet,1 Caroline Vanhulle,1 Richard Kettmann,3 Eric Verdin,2,dagger Arsène Burny,1,3 and Louis Droogmans1

Department of Molecular Biology, University of Brussels, B1640 Rhode-Saint-Genèse,1 and Faculty of Agronomy, B5030 Gembloux,3 Belgium, and The Picower Institute for Medical Research, Manhasset, New York 110302

Received 1 December 1997/Accepted 13 April 1998

Bovine leukemia virus (BLV) replication is controlled by both cis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication.

* Corresponding author. Mailing address: Université Libre de Bruxelles, Laboratoire de Chimie Biologique, rue des Chevaux 67, B-1640 Rhode-Saint-Genèse, Belgium. Phone: 32 2 6509826. Fax: 32 2 6509839. E-mail: vkiermer{at}dbm.ulb.ac.be.

dagger Present address: Gladstone Institute for Virology and Immunology, University of California---San Francisco, San Francisco, CA 94110.

J Virol, July 1998, p. 5526-5534, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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