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Cristina Cantale

The Viral Integrases


Introduction


Integrases are a class of endonucleases. An integrase is one of the characteristic proteins of retroviruses, a particular class of viruses that use RNA as genetic material. After infection, RNA has to be transcripted into viral DNA by a viral protein, Reverse Transcriptase, and finally inserted into the host genome. Integrases play a main role in the "insertion" of viral DNA into the host genome and this is considered a crucial event for replication and diffusion of infection.
As this "provirus" remains in the cellular genome and behaves as a part of the genetic material, this event is full of further consequences for the host, mainly during its own DNA recombination/transposition phases. More, if a germ cell is infected, the provirus can be transmitted to the progeny, where it can remain in an unexpressed form.
Studies of the molecular mechanism of this "integration",which have been carried out using a large ensemble of techniques could also have therapeutical implications if the integration could be proved to be it a compulsory step of infection. The development of drugs able to inhibit one of the various steps and/or components involved into "integration" could have profound implications for antiretroviral therapy. Indeed, Human Immunodeficiency Virus, HIV, the ethiological agent of AIDS, is a retrovirus.

Integration of viral DNA is reminescent of the ability of certain sequences to move from one site to another. From this point of view a retrovirus can be considered a transposable element like retrotransposones and trasposones. This similitude, even with different strategies and other minor details, shows in a very similar insertion mechanisms. Comparing sequences from transposable elements supplies a powerful tool to elucidate the evolution steps of retroviruses, retrotransposones and transposones.

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Last updated 25th Oct '96