In the August 6 issue of Nature, scientists show for the first time the structure of the entire HIV genome, using a relatively new technique that allows them to “see” how HIV-1 RNA folds.

HIV belongs to a class of viruses known as retroviruses. Retroviruses are different from other viruses in that their genes are composed of RNA (ribonucleic acid), not DNA (deoxyribonucleic acid). In order to replicate itself, HIV injects its genetic material (RNA) into the host.

Unlike DNA, RNA does not usually form a double helix. Instead, scientists have found that the genomes of RNA viruses contain folds that form higher ordered structures with motifs, or common patterns, that regulate viral replication.

To study these structures, scientists usually cut them out of HIV’s RNA and examine them individually. This method allows them to study these pieces of RNA very carefully to determine their structure and function, but its disadvantage is that only small portions of the HIV genome can be seen at once.

So far, most of the HIV RNA structures scientists have studied have functions related to regulation of replication and the final assembly of the virus.

In this paper, scientists have provided an overall “aerial” view of the structure of the HIV-1 RNA genome using an RNA analysis technology called SHAPE. This technique allows them to identify which parts of the HIV RNA are more flexible and floppy, and which parts are more rigid and structured. By also using known information about the sequence and how the building blocks of RNA bind to each other, this allowed the researchers to create a good estimate of how the entire RNA genome is folded.

In creating a model of the structure of the HIV-1 RNA genome, researchers found new, highly structured regions in the RNA genome that play a significant role in protein making and  folding. By studying this relationship between RNA and protein structure, researchers can determine the RNA regions that the virus uses to replicate its proteins.

Future drug development may focus on how information in RNA is translated into creating the structure of proteins. By inhibiting the creation of certain proteins, assembly of new viruses can be averted, and thus viral replication can be stopped.

Although the researchers of this study have discovered a great deal about the HIV-1 RNA genome, much more remains to be uncovered. In the future, scientists will likely hone in on more specific aspects of the RNA genome structure, thus identifying precise targets for new anti-HIV therapies.

For more information, please see the study in Nature (abstract).