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

Nathan D. Jones, Miguel A. Lopez, Jeungphill Hanne, Mitchell B. Peake, Jong-Bong Lee, Richard Fishel () and Kristine E. Yoder ()
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Nathan D. Jones: Immunology and Medical Genetics, The Ohio State University Medical Center
Miguel A. Lopez: 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)
Richard Fishel: Immunology and Medical Genetics, The Ohio State University Medical Center
Kristine E. Yoder: Immunology and Medical Genetics, The Ohio State University Medical Center

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11409

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