June 28, 2011
A new study has applied a powerful mathematical method that can pick out groups of many correlated units over time, at the genetic level, to determine which areas of HIV are most critically resistant to mutation. The researchers defined HIV genetic segments purely mathematically, without reference to their known functions, relying on random-matrix theory to filter out the "noise" of random correlations to find sectors of HIV that least tolerated mutations.
The method lent weight to previous research suggesting that part of the structural matrix comprising the capsid, or internal shell of the virus, was a key area to target. The HIV capsid is composed of a honeycomb-like structure, and a sector of the viral sequence called sector 3 of the gag protein helps form the edges of the honeycomb. If that sector were subjected to mutation, the structure would not interlock and the shell would collapse.
Among "elite controllers" -- rare patients whose bodies suppress HIV without drugs -- the immune system also most commonly targets sector 3, found study co-author Dr. Bruce Walker, director of the Ragon Institute. Even immune systems that fail to control HIV focus on sector 3, but waste their main assault on easily mutating areas of the virus.
The team's research only focused on "killer" T-cells, which attack HIV-infected cells. However, many researchers believe a successful vaccine also would have to mobilize antibodies that attack free-floating virus. Study co-author Dr. Arup Chakraborty, a professor of chemistry and chemical engineering at the Massachusetts Institute of Technology, is working with Dennis Burton, an HIV antibody expert at Scripps Research Institute, to apply random-matrix theory to antibody-based vaccines.
The full study, "Coordinate Linkage of HIV Evolution Reveals Regions of Immunological Vulnerability," was published ahead of the print edition of Proceedings of the National Academy of Sciences (2011;doi:10.1073/pnas.1105315108).
Wall Street Journal
06.21.2011; Mark Schoofs
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