AIDS entire genome decoded

For the first time, experts have decoded the structure of an entire HIV genome -a breakthroughthat will now help in finding the VIRUS weak spot. Scientistd will now able to peep right inside the deadly AIDS virus.

The work was done by Dr Kevin Weeks, a chemistry professor of the College of Arts and Sciences at the University of North Carolina (UNC) at Chapel Hill, and colleagues, and features as the cover story of the 6 August issue of Nature.

Before this work, researchers had only modelled small regions of the HIV genome, which is very large and made of two strands of nearly 10,000 building blocks or nucleotides each.

Viruses like HIV, whose genetic code is carried on RNA (rather than DNA) are harder to unravel because unlike DNA where the code is carried almost entirely in sequential building blocks or nucleotides, RNA folds into complex and intricate three-dimensional patterns that are harder to unravel. Other RNA-based viruses include the flu viruses, hepatitis C, the common cold, some cancer precursors, polio, and many others.

The replication of RNA-based viruses is controlled at many levels, including conserved "structures" of RNA genome, many of which have not been studied in much detail. The way the HIV encodes proteins is not straightforward either: while there is a correspondence between RNA and a primary sequencing of proteins, there is another level of coding between these "structures" and "inter-domain" loops that connect different parts of HIV proteins.

For the study, the researchers used a high-throughput RNA analyser called SHAPE to examine the architecture of HIV genomes isolated from infectious cultures containing trillions of viral particles.What they found suggests that the complex RNA structures (which they referred to as "motifs") influenced several steps in the HIV infectivity cycle, in other words they modulated "ribosome elongation to promote native protein folding".

They also found that: "Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs."

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.

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.