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Cristina Cantale
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).
PPS96
List of Contents
The Retroviruses
Integration
mechanismReferences
Last updated 25th Oct '96