The study was led by a team at the National Institute of Allergy and Infectious Diseases.
The HIV virus has numerous levels of defense but this protein component is stable and more importantly appears vulnerable to attack from this specific antibody, known as b12. The antibody is found in the blood of people whose immune systems appear to fight HIV for long periods of time.
In 1998, researchers published the first X-ray of the core of HIV gp120 as it attaches to a cellular receptor known as CD4. The researchers have now found that the gp120-CD4 encounter starts with a highly focused contact and then expands to a broader surface that stabilizes the interaction.
Until now, no one had succeeded in determining the detailed structure of b12 in complex with gp120. They saw that b12 binds gp120 at the same point where gp120 initially attaches to CD4.
Unlike the gp120-CD4 interactions, however, b12 can latch onto the site of CD4's first contact without requiring a shape change in gp120 to create a stable bond between the two molecules. Essentially, the scientists found that the initial point of CD4 contact is a site of gp120 weakness because it is the site of recognition, called an epitope, for b12.
“The structure of this gp120 epitope, and its susceptibility to attack by a broadly neutralizing antibody, shows us a critical area of vulnerability on the virus that we may be able to target with vaccines,” said Gary Nabel, director of NIAID's VRC.