UNC-CH researchers unravel HIV genome
Posted August 5, 2009
Chapel Hill, N.C. — Researchers at UNC-Chapel Hill have decoded the HIV genome for the first time, and the results could lead to advances in the fight against AIDS say the editors of the journal Nature.
Led by UNC-CH chemistry professor Kevin Weeks, the team published their findings in the Aug. 6 issue of Nature. Nature chose the study as its cover story “Inside HIV-1.”
“Insights from this work could lead to a better understanding of HIV-1 biology and to new antiretroviral interventions,” the editors of the prestigious international publication said in an editorial.
Nature’s view was echoed by Hashim Al-Hashimi, a professor of chemistry and biophysics at the University of Michigan.
“Structural biologists can now zoom in on these regions to explore their functions further,” Al-Hashimi said of the genome structure.
Weeks pointed out that the project could have wider implications by leading to a better understanding of how viruses work.
"We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host,” said Weeks, a professor of chemistry at UNC-CH’s College of Arts and Sciences.
Nature noted in its editorial that the UNC-CH work provided “total” analysis of the RNA.
“Secondary structures within single-stranded viral RNA genomes are known to serve functional and regulatory roles, but until now there has been no comprehensive analysis of total RNA for any virus,” the editors wrote.
The HIV genome is composed of two strands and includes nearly 10,000 nucleotides each, Weeks noted. HIV and viruses are composed of single-strand RNA rather than DNA, which is a double strand. Genetic information is contained in nucleotides, and it is more complex in RNA, Weeks noted.
In decoding the genome, the researches discovered that the RNA structures influence multiple steps in the HIV cycle of infectivity. The RNA folds back onto itself into three-dimensional objects.
"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.
Working with Weeks on the project were Joseph Watts, a chemistry postdoctoral fellow at UNC-CH’s Linberger Comprehensive Cancer Center, along with Christopher Leonard, Kristen Dang, Ron Swanstrom, and Christina Burch.
By successfully mapping the genome, Swanstrom said the RNA can be monitored. Mutations of viruses, especially HIV, make them difficult if not impossible to defeat.
"One approach is to change the RNA sequence and see if the virus notices," Swanstrom said. "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."
In his best-seller, “The Langauge of God,” Francis Collins noted the complexity of HIV.
“( R)apid evolutionary changes in the HIV virus that causes AIDS have provided a major challenge for vaccine development, and are the major cause of the ultimate relapse in those treated with drugs against AIDS,” wrote Collins, who earned his medical degree at UNC-CH and later led the human genome project.
The team studied HIV genomes from infectious cultures grown by Robert Gorelick and Julian Bess at the National Cancer Institute. The institute and the National Institutes of Health supported the study.