May 13, 2003
Typically, viruses 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 attaching and targeting the virus for destruction. In contrast, HIV-1 continuously changes the arrangement of large sugar molecules studded across its gp120/41 protein coat, thereby obstructing those docking regions for antibodies.
The research team, led by Howard Hughes Institute investigator George M. Shaw at the University of Alabama-Birmingham, termed the mechanism an evolving "glycan shield," and acknowledged the discovery was a surprise. Shaw and colleagues were equally 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," said Shaw.
The findings indicate that the immune system attempts to fight HIV, but "the glycan shield mutates at a faster rate than the immune system can change in order to keep up," according to Shaw. Despite the resourcefulness of HIV, Shaw indicated that there is hope for developing an effective vaccine for uninfected people. Of particular interest is the idea of combining an immunogen that elicits neutralizing antibodies with other compounds of the immune system, including cytotoxic T-lymphocytes.
Shaw emphasized that the newly discovered evolving glycan shield mechanism of antibody escape is but one of several ways in which HIV-1 is virally persistent in the face of an evolving antibody repertoire. "The trick," suggested Shaw, "will be to understand these multiple mechanisms more fully and to find the Achilles' heel."
The study, "Antibody Neutralization and Escape by HIV-1," was published in Nature (2003;422:307-312).
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