People with the ability to stave off AIDS for years after initial infection by HIV have been called "long-term non-progressors" or "elite controllers."
One component of this remarkable resistance comes from an individual's HLA genes. Long-term non-progressors tend to have HLA genes that help the immune system recognize and fight HIV more efficiently.
A team of researchers from the Emory Vaccine Center studying HIV-infected people with particularly effective HLA genes has observed how the virus mutates and evolves in response to immune pressure.
The observations, published in the Journal of Experimental Medicine, can provide guidance on what kinds of immune responses a successful HIV vaccine should generate.
The team was led by Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine, Emory Vaccine Center, and Yerkes National Primate Research Center. Hunter is a Georgia Research Alliance Eminent Scholar. First author Hayley Crawford, a graduate student at Oxford University, England, performed much of the research while working in Hunter's laboratory.
The Emory/Oxford team studied people in Zambia and South Africa with one form of the HLA gene that helps the immune system control HIV, called HLA-B*5703.
HLA genes encode molecules that display fragments of viral proteins, known as epitopes, on the surface of infected cells. When white blood cells known as cytotoxic T lymphocytes (CTLs) spot certain combinations of HLA molecules and viral epitopes, they attack the infected cells.
The authors show that a set of three mutations in HIV's Gag protein, which makes up the viral core, progressively slow viral replication. In cell culture, a triple-mutant virus replicates 20 times slower than normal. However, these same mutations effectively eliminate the ability of CTLs to detect the virus. so that in an infected person, once all three mutations are in pl
|Contact: Holly Korschun|