The study, published in the March 20, 2003, issue of the journal Nature, shows that HIV-1, a common strain of the virus that causes AIDS, uses a strategy not seen before in other viruses to escape attack by antibodies, one of the immune system's prime weapons against invading viruses and bacteria.
Viruses typically vary the protein sequence, or epitope, of the viral envelope that acts as a docking station for antibodies. This variation alters the docking region on the virus and prevents antibodies from grabbing hold and targeting the virus for destruction. HIV-1, in contrast, continuously changes the arrangement of large sugar molecules studded across its gp120/41 protein coat so that those docking regions for antibodies are obstructed.
The research team, led by Howard Hughes Medical Institute investigator George M. Shaw at the University of Alabama at Birmingham (UAB), dubbed the mechanism an evolving "glycan shield," and said the discovery was a surprise. Shaw and his colleagues were just as surprised at the rapidity and extent to which the replicating virus population in infected patients escaped antibody recognition.
"Before these findings, the role of antibodies in combating the virus that causes AIDS was not altogether clear. The new data suggest a more active role for HIV-1-neutralizing antibodies in virus containment and an unexpected mechanism of virus escape," he said.
"We found that the neutralizing epitopes on the virus did not change, but instead other parts of the viral envelope mutated, generally in a way that altered specific amino acids to which carbohydrates normally attach," Shaw said. "These changes in glycan molecules prevent the binding
Contact: Jim Keeley
Howard Hughes Medical Institute