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Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration

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  • Nathan D. Jones

    (Immunology and Medical Genetics, The Ohio State University Medical Center
    The Interdisciplinary Biophysics Graduate Program, The Ohio State University)

  • Miguel A. Lopez Jr

    (Immunology and Medical Genetics, The Ohio State University Medical Center)

  • Jeungphill Hanne

    (Immunology and Medical Genetics, The Ohio State University Medical Center)

  • Mitchell B. Peake

    (Immunology and Medical Genetics, The Ohio State University Medical Center)

  • Jong-Bong Lee

    (Pohang University of Science and Technology (POSTECH)
    Interdisciplinary Bioscience and Bioengineering, POSTECH)

  • Richard Fishel

    (Immunology and Medical Genetics, The Ohio State University Medical Center
    The Interdisciplinary Biophysics Graduate Program, The Ohio State University
    The Ohio State University)

  • Kristine E. Yoder

    (Immunology and Medical Genetics, The Ohio State University Medical Center)

Abstract

Retroviruses must integrate their linear viral cDNA into the host genome for a productive infection. Integration is catalysed by the retrovirus-encoded integrase (IN), which forms a tetramer or octamer complex with the viral cDNA long terminal repeat (LTR) ends termed an intasome. IN removes two 3′-nucleotides from both LTR ends and catalyses strand transfer of the recessed 3′-hydroxyls into the target DNA separated by 4–6 bp. Host DNA repair restores the resulting 5′-Flap and single-stranded DNA (ssDNA) gap. Here we have used multiple single molecule imaging tools to determine that the prototype foamy virus (PFV) retroviral intasome searches for an integration site by one-dimensional (1D) rotation-coupled diffusion along DNA. Once a target site is identified, the time between PFV strand transfer events is 470 ms. The majority of PFV intasome search events were non-productive. These observations identify new dynamic IN functions and suggest that target site-selection limits retroviral integration.

Suggested Citation

  • Nathan D. Jones & Miguel A. Lopez Jr & Jeungphill Hanne & Mitchell B. Peake & Jong-Bong Lee & Richard Fishel & Kristine E. Yoder, 2016. "Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11409
    DOI: 10.1038/ncomms11409
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    Cited by:

    1. Gayan Senavirathne & James London & Anne Gardner & Richard Fishel & Kristine E. Yoder, 2023. "DNA strand breaks and gaps target retroviral intasome binding and integration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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