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No-entry zones for AIDS virus
Date:11/12/2009

o the right" of them.

"For the first time we have very precisely defined areas in the human genome where HIV hardly ever integrates," Giordano explains. The scientists are electrified by the result, because there must be a reason why HIV evades these sites. "We assume that there is a particular mechanism at work which blocks the way for the virus," says Giordano. "On the other hand, it is also possible that some factor that HIV needs for its integration is missing at these sites." The researchers even know already that this access barrier cannot be an unspecific one: "Other retroviruses even prefer to insert their genetic material exactly at the transcription start sites," Laufs explains. "Therefore, we assume that the mechanism protecting the transcription start sites of active genes from HIV genome integration very specifically prevents HIV integration." For example, this mechanism might block the work of an enzyme called integrase, which is responsible for integrating the viral DNA into the DNA of the infected cell.

This enzyme is currently in the focus of the search for an improved AIDS therapy. The highly active treatment available today attacks the virus from several different angles using different drugs: Reverse transcriptase inhibitors prevent the viral genome from being copied. Protease inhibitors block the maturation of new viral proteins. Scientists agree, however, that the best way of fighting the severe immune deficiency is to prevent integration of the viral genetic material into the DNA of the host cells. Substances preventing this, called integrase inhibitors, have been used in recent years, but the viruses have already started evading their effect through mutations. Therefore, virologists are urgently searching for new approaches to blocking this key enzyme of the virus. The mechanism that prevents HIV from integrating at the transcription start site might be a molecular model for developing such substances.


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Contact: Dr. Sibylle Kohlstaedt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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