Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 26, 2017; 8(1): 32-44
Published online Feb 26, 2017. doi: 10.4331/wjbc.v8.i1.32
Retroviral integrase protein and intasome nucleoprotein complex structures
Julia Grawenhoff, Alan N Engelman
Julia Grawenhoff, Alan N Engelman, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, United States
Julia Grawenhoff, Alan N Engelman, Department of Medicine, Harvard Medical School, Boston, MA 02115, United States
Author contributions: Grawenhoff J and Engelman AN conceived the review and wrote the manuscript.
Supported by United States National Institutes of Health grant, No. R01AI070042.
Conflict-of-interest statement: Authors declare no conflicts of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alan N Engelman, PhD, Professor of Medicine, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, CLS-1010, Boston, MA 02215, United States. alan_engelman@dfci.harvard.edu
Telephone: +1-617-6324361 Fax: +1-617-6324338
Received: November 1, 2016
Peer-review started: November 4, 2016
First decision: December 14, 2016
Revised: December 24, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: February 26, 2017
Abstract

Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase (IN) protein. IN catalyzes two distinct chemical reactions: 3’-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3’-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus (PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus (RSV) and β-retrovirus mouse mammary tumor virus (MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.

Keywords: DNA integration, 3-dimensional structure, Integrase, Intasome, Mouse mammary tumor virus, Retrovirus, Rous sarcoma virus, Prototype foamy virus, Human immunodeficiency virus/acquired immune deficiency syndrome

Core tip: This review examines the history of retroviral integrase structural biology and covers the currently available high-resolution structures of retroviral intasomes in detail. We in particular focus on the similarities and differences among the intasome structures of prototype foamy virus, Rous sarcoma virus and mouse mammary tumor virus.