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Annual Review of Virology

Volume 2, 2015

Retroviral Integrase: Then and Now

Abstract

The retroviral integrases are virally encoded, specialized recombinases that catalyze the insertion of viral DNA into the host cell's DNA, a process that is essential for virus propagation. We have learned a great deal since the existence of an integrated form of retroviral DNA (the provirus) was first proposed by Howard Temin in 1964. Initial studies focused on the genetics and biochemistry of avian and murine virus DNA integration, but the pace of discovery increased substantially with advances in technology, and an influx of investigators focused on the human immunodeficiency virus. We begin with a brief account of the scientific landscape in which some of the earliest discoveries were made, and summarize research that led to our current understanding of the biochemistry of integration. A more detailed account of recent analyses of integrase structure follows, as they have provided valuable insights into enzyme function and raised important new questions.

Keyword(s): core dimer, intasome, integrase, prophage, provirus, reaching dimer

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/content/journals/10.1146/annurev-virology-100114-055043
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Retroviral Integrase: Then and Now
Annual Review of Virology 2, 241 (2015); https://doi.org/10.1146/annurev-virology-100114-055043
/content/journals/10.1146/annurev-virology-100114-055043
/content/journals/10.1146/annurev-virology-100114-055043
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Supplemental Material

    Assembly of the prototype foamy virus (PFV) intasome (see ). This brief video portrays one possible scenario for how the PFV intasome may be assembled from PFV integrase (IN) monomers, the predominant multimer found in solution. The complex is shown in ribbon representation, with the inner subunits in red and blue. Viral DNA oligonucleotides are in orange ribbon ladder representation and the target DNA in yellow and black. The outer IN subunits only show the catalytic core domains and are colored gray. After the target DNA moves into place, the view zooms in to one active site to show the location of active site metals (depicted as green spheres) and the DDE residues (shown in stick representation) that are required for metal binding. This video was generated using UCSF Chimera software [Pettersen et al., 25:1605–12 (2004)] with the coordinates of PDB 4E7K.

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