This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Verhoef, K.
Right arrow Articles by Berkhout, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verhoef, K.
Right arrow Articles by Berkhout, B.

 Previous Article  |  Next Article 

Journal of Virology, February 1999, p. 1331-1340, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evolution of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat Promoter by Conversion of an NF-kappa B Enhancer Element into a GABP Binding Site

Koen Verhoef,1 Rogier W. Sanders,1 Veronique Fontaine,2 Shigetaka Kitajima,3 and Ben Berkhout1,*

Department of Human Retrovirology1 and Department of Medical Microbiology,2 Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands, and Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyou-ku 113, Tokyo, Japan3

Received 30 July 1998/Accepted 30 October 1998

Human immunodeficiency virus type 1 (HIV-1) transcription is regulated by the viral Tat protein and cellular factors, of which the concentration and activity may depend on the cell type. Viral long terminal repeat (LTR) promoter sequences are therefore optimized to suit the specific nuclear environment of the target host cell. In long-term cultures of a Tat-defective, poorly replicating HIV-1 mutant, we selected for a faster-replicating virus with a 1-nucleotide deletion in the upstream copy of two highly conserved NF-kappa B binding sites. The variant enhancer sequence demonstrated a severe loss of NF-kappa B binding in protein binding assays. Interestingly, we observed a new binding activity that is specific for the variant NF-kappa B sequence and is present in the nuclear extract of unstimulated cells that lack NF-kappa B. These results suggest that inactivation of the NF-kappa B site coincides with binding of another transcription factor. Fine mapping of the sequence requirements for binding of this factor revealed a core sequence similar to that of Ets binding sites, and supershift assays with antibodies demonstrated the involvement of the GABP transcription factor. Transient transfection experiments with LTR-chloramphenicol acetyltransferase constructs indicated that the variant LTR promoter is specifically inhibited by GABP in the absence of Tat, but this promoter was dramatically more responsive to Tat than the wild-type LTR. Introduction of this GABP site into the LAI virus yielded a specific gain of fitness in SupT1 cells, which contain little NF-kappa B protein. These results suggest that GABP potentiates Tat-mediated activation of LTR transcription and viral replication in some cell types. Conversion of an NF-kappa B into a GABP binding site is likely to have occurred also during the worldwide spread of HIV-1, as we noticed the same LTR modification in subtype E isolates from Thailand. This typical LTR promoter configuration may provide these viruses with unique biological properties.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5664822. Fax: 31-20-6916531. E-mail: b.berkhout{at}amc.uva.nl.

Journal of Virology, February 1999, p. 1331-1340, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • van Opijnen, T., Boerlijst, M. C., Berkhout, B. (2006). Effects of random mutations in the human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments.. J. Virol. 80: 6678-6685 [Abstract] [Full Text]  
  • Ranjbar, S., Rajsbaum, R., Goldfeld, A. E. (2006). Transactivator of Transcription from HIV Type 1 Subtype E Selectively Inhibits TNF Gene Expression via Interference with Chromatin Remodeling of the TNF Locus. J. Immunol. 176: 4182-4190 [Abstract] [Full Text]  
  • Desfosses, Y., Solis, M., Sun, Q., Grandvaux, N., Van Lint, C., Burny, A., Gatignol, A., Wainberg, M. A., Lin, R., Hiscott, J. (2005). Regulation of Human Immunodeficiency Virus Type 1 Gene Expression by Clade-Specific Tat Proteins. J. Virol. 79: 9180-9191 [Abstract] [Full Text]  
  • Maury, W., Thompson, R. J., Jones, Q., Bradley, S., Denke, T., Baccam, P., Smazik, M., Oaks, J. L. (2005). Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism. J. Virol. 79: 5653-5664 [Abstract] [Full Text]  
  • Lemieux, A.-M., Pare, M.-E., Audet, B., Legault, E., Lefort, S., Boucher, N., Landry, S., van Opijnen, T., Berkhout, B., Naghavi, M. H., Tremblay, M. J., Barbeau, B. (2004). T-cell Activation Leads to Poor Activation of the HIV-1 Clade E Long Terminal Repeat and Weak Association of Nuclear Factor-{kappa}B and NFAT with Its Enhancer Region. J. Biol. Chem. 279: 52949-52960 [Abstract] [Full Text]  
  • van Opijnen, T., Kamoschinski, J., Jeeninga, R. E., Berkhout, B. (2004). The Human Immunodeficiency Virus Type 1 Promoter Contains a CATA Box Instead of a TATA Box for Optimal Transcription and Replication. J. Virol. 78: 6883-6890 [Abstract] [Full Text]  
  • Ristevski, S., O'Leary, D. A., Thornell, A. P., Owen, M. J., Kola, I., Hertzog, P. J. (2004). The ETS Transcription Factor GABP{alpha} Is Essential for Early Embryogenesis. Mol. Cell. Biol. 24: 5844-5849 [Abstract] [Full Text]  
  • van Opijnen, T., Jeeninga, R. E., Boerlijst, M. C., Pollakis, G. P., Zetterberg, V., Salminen, M., Berkhout, B. (2004). Human Immunodeficiency Virus Type 1 Subtypes Have a Distinct Long Terminal Repeat That Determines the Replication Rate in a Host-Cell-Specific Manner. J. Virol. 78: 3675-3683 [Abstract] [Full Text]  
  • Rohr, O., Marban, C., Aunis, D., Schaeffer, E. (2003). Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J. Leukoc. Biol. 74: 736-749 [Abstract] [Full Text]  
  • Naghavi, M. H., Estable, M. C., Schwartz, S., Roeder, R. G., Vahlne, A. (2001). Upstream stimulating factor affects human immunodeficiency virus type 1 (HIV-1) long terminal repeat-directed transcription in a cell-specific manner, independently of the HIV-1 subtype and the core-negative regulatory element. J. Gen. Virol. 82: 547-559 [Abstract] [Full Text]  
  • Jeeninga, R. E., Hoogenkamp, M., Armand-Ugon, M., de Baar, M., Verhoef, K., Berkhout, B. (2000). Functional Differences between the Long Terminal Repeat Transcriptional Promoters of Human Immunodeficiency Virus Type 1 Subtypes A through G. J. Virol. 74: 3740-3751 [Abstract] [Full Text]  
  • Verhoef, K., Berkhout, B. (1999). A Second-Site Mutation That Restores Replication of a Tat-Defective Human Immunodeficiency Virus. J. Virol. 73: 2781-2789 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»