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Cristina Cantale

The Viral Integrases

The Integrase Protein

A bit of history

Integrase is an approximately 40kDa protein, encoded by the 3' end of the pol gene of retroviruses.
In studies and experiments carried out on Avian retroviruses in the early 80's (Grandganett D. P. et al, 86) it was recognized that integrases are involved in the integration process of viral DNA into host genome.
From 1987 to 1989 more evidence confirmed these first suggestions (Brown P.O. et al, 87 - Fujiwara T. and Mizuuchi K., 88).
In 1989 Bowerman obtained the integration of viral DNA into a target DNA in a in vitro system using a nucleoprotein complex recovered in the cytoplasm of MLV (Murine Leukemia virus) acutely infected cells after viral DNA synthesis (Bowerman B. et al, 89 and also Brown P.O. et al., 89).
A general model for integration started to be outlined.
Linear viral DNA present in PIC (PreIntegration Complex) is the precursor of integrated DNA. It is cleaved at 3' ends and these recessed ends are integrated in cell DNA, cut in a staggered fashion (about 5 bp which are then duplicated at the integration site), presumably by cellular DNA repair enzymes. This joining reaction doesn't require any exogenous source of energy.
The central role of Integrase proteins in the above model was demonstrated by Katz and coworkers in 1990. In their experiments, purified 32 kDa ASLV IN (Avian Sarcoma-Leukosis virus) alone was able to perform both the breakage and the joining reactions, using, as substrates, synthetic oligonucleotides mimicking LTR (Katzman et al.,89 - Katz R.A. et al, 90).
The same results were obtained using HIV in a similar in vitro system (Bushman F.D. et al., 90 - Vink C. et al., 91-1).

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Last updated 25th Oct '96