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Related Experiment Videos

HIV-1 LTR DNA sequence variation in brain-derived isolates

J R Corboy1, P J Garl

  • 1University of Colorado Health Sciences Center, Department of Neurology, Denver 80262, USA.

Journal of Neurovirology
|January 7, 1998
PubMed
Summary

Human immunodeficiency virus (HIV-1) central nervous system (CNS) isolates show distinct long terminal repeat (LTR) variations compared to blood isolates. These LTR differences may influence viral gene expression within the brain.

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Area of Science:

  • Virology
  • Neuroscience
  • Genetics

Background:

  • Human immunodeficiency virus (HIV-1) isolates from the central nervous system (CNS) exhibit distinct characteristics compared to blood-derived strains.
  • Macrophage tropism in CNS isolates is partly due to envelope glycoprotein gene variations, but long terminal repeat (LTR) differences may also affect gene expression.

Purpose of the Study:

  • To investigate the sequence variations within the HIV-1 LTR in brain-derived isolates.
  • To compare CNS-derived LTR sequences with published blood-derived LTR sequences.

Main Methods:

  • Sequencing of the HIV-1 LTR (bases -374 to +43) from brain tissue of four HIV-1-infected patients.
  • Analysis of 56 LTR clones from gray and white matter.
  • Comparison of sequenced clones with 17 published LTR sequences.

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Main Results:

  • Five distinct LTR quasispecies were identified within the brain samples.
  • Significant sequence variation was observed within and between brains, comparable to envelope glycoprotein quasispecies.
  • Most variations occurred upstream of NF-kappa B binding sites, with several unique substitutions altering NF-AT and LEF-1 binding sites compared to blood-derived LTRs.

Conclusions:

  • HIV-1 LTRs from the CNS exhibit unique sequence variations compared to blood-derived LTRs.
  • These variations, particularly in transcription factor binding sites, may contribute to cell-specific gene expression differences in the CNS.
  • Further research is needed to link specific LTR variations to differential gene expression in the CNS.