London, Feb 1 (Inditop.com) Researchers have cracked a key riddle that has foxed scientists for decades, potentially opening the way to better treatment of HIV, says a new study.
Imperial College London and Harvard University researchers have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV.
When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.
Prior to the new study, funded by the Medical Research Council and the US National Institutes of Health, many researchers had tried and failed to work out the 3-D structure of integrase bound to viral DNA.
New antiretroviral drugs for HIV work by blocking integrase, but scientists did not understand exactly how these drugs were working or how to improve them.
Researchers can only determine the structure of this kind of molecular machinery by obtaining high quality crystals.
For the new study, researchers grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.
Over the course of four years, the researchers carried out over 40,000 trials, out of which they were able to grow just seven kinds of crystals. Only one of these was of sufficient quality to allow determination of the 3-D structure.
Peter Cherepanov, who led the study at the Department of Medicine at Imperial College, said: “It is a truly amazing story. When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago.”
“Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallisation,” said Cherepanov, according to an Imperial College release.
“Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded,” he added.
The study was published in Nature.
