Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
DOI: 10.1017/S1462399407000257; 26 February 2007
Nick Vandegraaff and Alan Engelman (2007) Molecular mechanisms of HIV integration and therapeutic intervention. Expert Rev. Mol. Med. Vol. 9, Issue 6, DOI: 10.1017/S1462399407000257

Molecular mechanisms of HIV integration and therapeutic intervention

Nick Vandegraaff ^a1 and Alan Engelman ^{a2 c1}

^a1 Avexa Limited, Richmond, Victoria 3121, Australia.

^a2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.

^c1 Corresponding author: Alan Engelman, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. Tel: +1 617 632 4361; Fax: +1 617 632 3113; E-mail: alan_engelman@dfci.harvard.edu

Retroviruses, such as human immunodeficiency virus type 1 (HIV-1), are plus-sense RNA viruses that require reverse transcription and then DNA integration to establish a chromosomal provirus as an obligate replication intermediate. The viral enzyme reverse transcriptase synthesises linear double-stranded cDNA, which is the template for the viral enzyme integrase. Integrase catalyses two separate chemical reactions: an initial 3' processing of the nascent cDNA ends, which is followed in the cell nucleus by their covalent attachment to the 5' phosphates of a double-stranded staggered cut in chromosomal DNA. As integrase activity is essential for productive retroviral infection, there is intense interest in developing small-molecule inhibitors of the HIV-1 enzyme to increase the breadth of the antiviral arsenal used to fight HIV/AIDS. Purified integrase protein displays the 3' processing and DNA-strand-transfer activities essential for cDNA integration in integration assays in vitro, but numerous studies indicate that cellular proteins play important roles during integration in infected cells. This review highlights the molecular mechanisms behind HIV-1 integration, focusing on recent insights into functions of human cellular cofactors. The progress towards developing integrase inhibitors for their use in the clinic is also reviewed.

Full text online (purchase or subscribe through Cambridge Journals Online)

| home | search | glossary | links | sitemap | contact |

Expert Reviews in Molecular Medicine © Cambridge University Press ISSN 1462-3994 (Disclaimer and copyright)
Editorial Office: Centre for Applied Research in Educational Technologies (CARET), 1st Floor, 16 Mill Lane, Cambridge, CB2 1SB, UK. Tel: +44 (0)1223 765 375; Fax: +44(0)1223 765 505; E-mail: ermm@caret.cam.ac.uk