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Renée Marije van der Sluis

An AP-1 binding site in the enhancer/core element of the HIV-1 promoter controls the ability of HIV-1 to establish latent infection

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  • Alexandra Duverger, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA, USA
  • Frank Wolschendorf, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Mingce Zhang, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Frederic Wagner, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Brandon Hatcher, Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Jennifer Jones, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Randall Q. Cron, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • ,
  • Renée Marije van der Sluis
  • Rienk E. Jeeninga, Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
  • ,
  • Ben Berkhout, Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
  • ,
  • Olaf Kutsch, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
Following integration, HIV-1 in most cases produces active infection events; however, in some rare instances, latent infection events are established. The latter have major clinical implications, as latent infection allows the virus to persist despite antiretroviral therapy. Both the cellular factors and the viral elements that potentially determine whether HIV-1 establishes active or latent infection events remain largely elusive. We detail here the contribution of different long terminal repeat (LTR) sequences for the establishment of latent HIV-1 infection. Using a panel of full-length replication-competent virus constructs that reflect naturally occurring differences of HIV-1 subtype-specific LTRs and targeted LTR mutants, we found the primary ability of HIV-1 to establish latent infection in this system to be controlled by a four-nucleotide (nt) AP-1 element just upstream of the NF-κB element in the viral promoter. Deletion of this AP-1 site mostly deprived HIV-1 of the ability to establish latent HIV-1 infection. Extension of this site to a 7-nt AP-1 sequence massively promoted latency establishment, suggesting that this promoter region represents a latency establishment element (LEE). Given that these minimal changes in a transcription factor binding site affect latency establishment to such large extent, our data support the notion that HIV-1 latency is a transcription factor restriction phenomenon.
OriginalsprogEngelsk
TidsskriftJournal of Virology
Vol/bind87
Nummer4
Sider (fra-til)2264-2277
ISSN0022-538X
DOI
StatusUdgivet - feb. 2013
Eksternt udgivetJa

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