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Retroviruses

Integration hotspots for disease?

Nature Reviews Microbiology volume 6, page 333 (2008)Cite this article

Retroviruses persist in a dormant state in host cells by integrating copies of their genome (provirus) into host chromosomes. The integration process is not random, as there is a specific consensus integration sequence for each retrovirus and the pattern of integration sites varies: HIV favours integration into active genes, whereas murine leukaemia virus favours integration into the 5′ end of genes. In this report, Meekings et al. compared the integration of HTLV-1 in vitro, in the absence of immune selection, and in vivo, where the host immune response exerts a selective pressure on viral replication.

Sites of HTLV-1 integration were pinpointed using linker-mediated PCR and sequencing. The distribution of integration sites was compared with the distribution of random control sites. Statistical analyses were used to interrogate datasets and deduce the favoured integration sites under different conditions. Comparison of integration sites in cultured human lymphocytes and peripheral blood mononuclear cells (PBMCs) isolated from infected individuals showed that HTLV-1 integrates at the same sequence-specific target sites in host chromosomes in vitro and in vivo. The in vitro integration data generated by Meekings et al. confirmed the conclusions of a recent study by Derse and colleagues — HTLV-1 preferentially integrates into transcriptionally active regions of chromosomes in vitro, including genes and CpG islands. But the picture during infection was markedly different: HTLV-1 integrated into transcriptionally active regions of the chromosomes far more often in PBMCs from infected individuals compared with cultured cells, although proviruses in PBMCs were far less likely to be found in genes than were proviruses in cultured cells.

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References

ORIGINAL RESEARCH PAPER

  1. Meekings, K. N., Leipzig, J., Bushman, F. D., Taylor, G. P. & Bangham C. R. M. HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP. PLoS Pathog. 4, e1000027 (2008)

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FURTHER READING

  1. Derse, D. et al. Human T-cell leukemia virus type 1 integration target sites in the human genome: comparison with those of other retroviruses. J. Virol. 81, 6731–6741 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bushman, F. et al. Genome-wide analysis of retroviral DNA integration. Nature Rev. Microbiol. 3, 848–858 (2005)

    Article  CAS  Google Scholar 

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Authors
  1. Susan Jones
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Jones, S. Integration hotspots for disease?. Nat Rev Microbiol 6, 333 (2008). https://doi.org/10.1038/nrmicro1907

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  • DOI: https://doi.org/10.1038/nrmicro1907

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