Case cracked: Team decodes HIV genome structure

UNC-CHAPEL HILL (US) — Researchers for the first time have decoded the structure of a complete HIV genome. The results have widespread implications for understanding the strategies that viruses, like the one that causes AIDS, use to infect humans.

The study by researchers at the University of North Carolina at Chapel Hill—featured on the cover of the August 6 issue of the journal Nature—opens the door for further research that may accelerate the development of antiviral drugs.

Much like the viruses that cause influenza, hepatitis C and polio, HIV carries its genetic information as single-stranded RNA rather than double-stranded DNA. The information encoded in DNA is almost entirely in the sequence of its building blocks, which are called nucleotides.

But the information encoded in RNA is more complex; RNA is able to fold into intricate patterns and structures. These structures are created when the ribbon-like RNA genome folds back on itself to make three-dimensional objects.

Study leader Kevin Weeks, a professor of chemistry, says prior to this new work researchers had modeled only small regions of the HIV RNA genome. The HIV RNA genome is very large, composed of two strands of nearly 10,000 nucleotides each.

Weeks and Joseph M. Watts, a chemistry postdoctoral fellow, used technology developed by Weeks’ lab to analyze the architecture of HIV genomes isolated from infectious cultures containing trillions of viral particles that were grown by Robert Gorelick and Julian Bess of the National Cancer Institute.

They then teamed up with UNC researchers for further analysis and found that the RNA structures influence multiple steps in the HIV infectivity cycle.

“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,” says Weeks.

Ron Swanstrom, a professor of microbiology and immunology, and Weeks note that the study is the key to unlocking additional roles of RNA genomes that are important to the lifecycle of these viruses in future investigations.

“One approach is to change the RNA sequence and see if the virus notices,” Swanstrom says. “If it doesn’t grow as well when you disrupt the virus with mutations, then you know you’ve mutated or affected something that was important to the virus.”

Weeks adds: “We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host.”

The study was supported by the National Institutes of Health and the National Cancer Institute.

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