Volume 6 Supplement 2

Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Open Access

The AP-1 binding sites located in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivity

  • Nathalie Vandenhoudt1,
  • Stéphane de Walque1,
  • Benoît Van Driessche1,
  • Laurence Colin1,
  • Valérie Martinelli1,
  • Allan Guiguen1,
  • Caroline Vanhulle1,
  • Arsène Burny1,
  • Georges Herbein2,
  • Olivier Rohr3 and
  • Carine Van Lint1
Retrovirology20096(Suppl 2):P89

DOI: 10.1186/1742-4690-6-S2-P89

Published: 24 September 2009

We have previously identified three AP-1 binding sites in the pol gene of human immunodeficiency virus type 1 (HIV-1) and shown that short oligonucleotides containing these sites functioned as phorbol ester-inducible enhancers (Van Lint et al., 1991, J. Virol., 65:7066-7072). These sites are located in a region, called fragment 5103, exhibiting a phorbol ester-inducible enhancing activity on the viral thymidine kinase promoter in HeLa cells. In this study, we have further characterized each of the AP-1 binding sites and have shown that transcription factors c-Fos, JunB and JunD interacted in vitro with these motifs. For each site, we have identified mutations abolishing AP-1 factor binding without altering the underlying amino acid sequence of the HIV-1 reverse transcriptase. By transient transfection assays, we have demonstrated that the intragenic AP-1 binding sites were entirely responsible for the PMA-dependent transcriptional activity of fragment 5103. Moreover, this PMA-stimulated activity of fragment 5103 was inhibited by a dominant-negative A-Fos mutant provided the AP-1 sites were not mutated. Finally, we have investigated the biological significance of the intragenic AP-1 binding sites in HIV-1 replication and have shown that these sites are important for viral infectivity.

Authors’ Affiliations

(1)
Laboratory of Molecular Virology, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles (ULB)
(2)
Department of Virology, University of Franche-Comte, St-Jacques Hospital
(3)
INSERM U575, Virology Institute

Copyright

© Vandenhoudt et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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