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Related Experiment Videos

Promoter evolution in BK virus: functional elements are created at sequence junctions.

R B Markowitz1, S Tolbert, W S Dynan

  • 1Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.

Journal of Virology
|May 1, 1990
PubMed
Summary
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BK virus (BKV) gene expression is low in archetypal strains but high in rearranged strains. Newly created AP-1 binding enhancer modules in rearranged BKV strains activate early gene expression.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • BK virus (BKV) is a human polyomavirus with two main forms: archetypal and rearranged.
  • Archetypal BKV exhibits limited early gene expression, hindering viral replication and pathogenesis.
  • Rearranged BKV strains possess distinct genetic features that influence their biological activity.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the differential gene expression between archetypal and rearranged BK virus strains.
  • To identify specific genetic elements responsible for the enhanced early gene expression observed in rearranged BKV.
  • To understand how sequence alterations in BKV impact viral promoter activity.

Main Methods:

  • Comparative analysis of gene expression levels between archetypal and rearranged BKV strains.

Related Experiment Videos

  • Detailed sequence analysis of rearranged BKV genomes to identify novel regulatory elements.
  • Functional assays to assess the impact of identified enhancer modules on viral early gene expression.

    • Main Results:

    • Archetypal BKV strains demonstrated significantly lower early gene expression compared to rearranged strains.
    • A specific rearranged laboratory strain contained novel AP-1 binding enhancer modules at the junction of sequence repeats.
    • Introduction of these novel enhancer sequences into the archetypal BKV genome activated its previously quiescent early promoter.

    Conclusions:

    • Sequence rearrangements, particularly the acquisition of AP-1 binding enhancer modules, are critical for activating early gene expression in BK virus.
    • These enhancer elements play a key role in overcoming the transcriptional repression observed in archetypal BKV strains.
    • Understanding these regulatory mechanisms provides insights into BKV pathogenesis and potential therapeutic targets.