New genetic mapping of AIDS may offer clues

WASHINGTON - A new technique has given researchers a "big picture" look at the genome of the AIDS virus, the first time its entire gene map has been decoded.

The technique may not only lead to new treatments against the fatal and incurable virus, but for other viruses such as influenza and the bugs that cause the common cold, they said on Wednesday.

"We are hopeful that this is going to open up many new opportunities for drug discovery," Kevin Weeks of the University of North Carolina, who led the research, said in a telephone interview. "We have a big list of things we can try."

The human immunodeficiency virus or HIV is what is known as an RNA virus. Like influenza, polio and many viruses that cause colds, it uses RNA instead of DNA as its map when carrying out functions.

DNA depends on building blocks called nucleotides to carry information on its two strands. These are the familiar A, C, T and G of the genetic code. RNA has just one strand and depends on complex folding patterns to carry information, as well as nucleotides.

"There is so much structure in the HIV RNA genome that it almost certainly plays a previously unappreciated role in the expression of the genetic code," Weeks said.

His team developed a new chemical method called SHAPE to make an image not only of the RNA's nucleotides, but of the shapes and folds of the RNA strands.

Other imaging methods such as X-ray crystallography can capture the precise position of each atom, but only one small area at a time. SHAPE gets a bigger picture, but not at the atomic level, Weeks said.

"The technique is thus akin to zooming out on a map and getting a broader view of the landscape at the expense of fine details," Hashim Al-Hashimi of the University of Michigan wrote in a commentary on the findings, published in Nature.

This, in turn, will help researchers make better drugs to treat such viruses, said Weeks. New drugs are often engineered to fit into specific structures on a virus, blocking it from attaching to a cell, for instance, or gumming up its works so it cannot replicate.

But RNA viruses are especially hard to defend against.

More than 20 drugs are now on the market for HIV, for instance, and it requires various combinations to keep it in check. Many strains of flu resist the effects of older antivirals and mutations help one strain of seasonal influenza resist Roche AG's Tamiflu.

Weeks said the new imaging technique will help researchers looking for new approaches. "In the short term it almost certainly is going to make it easier to design short, interfering RNAs," he said.

These drugs, known as siRNAs for short, stop RNA from functioning and can interfere with defective cells or bacteria and viruses.

Companies such as Merck and Co. and Silence Therapeutics Plc are working to use this approach.

"SiRNAs can be very potent," Weeks said. "They are expensive to make but they are relatively easy to design."

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