Scientists have made a major advance in the field of AIDS research; they have decoded the entire structure of an HIV genome.  The investigators say the work offers clues as to the behavior of the AIDS virus and could lead to the development of new drugs to treat the disease.

The AIDS virus has proved to be a daunting foe to scientists who, for decades, have tried to understand HIV's ability to evade the body's immune system so drugs can be developed to stop progression of the disease.

Now, scientists at the University of North Carolina Chapel Hill (UNCCH) have decoded the entire HIV genome, a feat experts say should make it easier for AIDS researchers to understand the behavior of the AID's virus and could lead to the development of new, anti-viral drugs.
Kevin Weeks, a professor of chemistry at UNCCH, led the effort to decipher the HIV genome, comprised of a ribbon-like RNA strand made up of intricate patterns or genetic structures that instruct the virus on how to behave.

"The HIV genome is chock full of RNA structures," he said.  "And these RNA structures have major biological roles.  There are many, many structures and these structures regulate the genome that we had just not appreciated prior to this work."

For Weeks, the most striking discovery is the vast number of RNA structures that influence that virus's lifecycle, controlling how HIV infects humans and how rapidly it reproduces itself.

Unlike DNA - which contains sequences of genetic building blocks that regulate the biological functions of living organisms - viruses are not living.  They get their genetic instructions from RNA, which folds into intricate patterns that form complex structures.

The HIV genome is enormous compared to the polio and hepatitis C viruses. It contains two strands of ten thousand building blocks each.
Until now, Weeks says only small portions of the complex loops and patterns that make up HIV's huge genome could be studied.
So, after isolating RNA from trillions of viral particles grown in the laboratory, Weeks and colleagues used a technology they'd developed that gave them an aerial view of the viruses' genome.

"You know, it's a little bit like the famous story of several people who investigated the elephant," Weeks explained.  "Sometimes if you look at only pieces of something you miss the big picture.  So, the fact that the genome is [a] pretty large size means it was hard to get a big picture view, and the technology that we created for this work made it possible to get a whole, holistic view of the genome at the same time."

 Weeks says there are both short-term and long-term implications of having the entire HIV genome sequence in hand.

 "When we have a good understanding of these structures, it makes it a lot easier to interfere with how these structures function," he added.  "And when we are able to interfere with how these structures function with say small molecules or bio-deliverable molecules, we call those drugs.  So, this work does not create any drugs for next month or next year.  But I think this kind of structural information will motivate exploration of whether it's possible to make drugs directed directly at the genome of RNA viruses."

Hepatitis C, polio and influenza viruses are also programmed by an RNA genome, raising the possibility that researchers could use the same technology to better understand the biology of these diseases.

An article describing the complete genetic sequence of the AIDS virus is published this week in the journal Nature.