Sunday, January 21, 2007

Neutralizing antibodies drive HIV mutation

Gnome writes "HIV mutants accumulate rapidly due to a short generation time, a sloppy replication mechanism, and the large number of viruses within the host. The viral envelope (env) gene mutates especially quickly (1-2% per year) because of the selective pressure of neutralizing antibodies. The resulting heterogeneity poses a challenge to vaccine development. Frost and colleagues sought to understand the patterns of rapid mutation and escape by analyzing 13 people recently infected with HIV. They compared the initial env sequence with sequences obtained at yearly intervals and measured neutralizing antibodies in the blood. They found that HIV escape from neutralizing antibodies strongly correlated with changes in the amino acid sequence of env. Escape did not correlate with changes in N-linked glycosylation sites or insertions or deletions (indels). Their data support a simple model for escape from neutralizing antibodies proposed by Haraguchi and Sasaki, which incorporates cross-reactivity. The inability of the immune system to 'catch up' with the continually escaping virus is an example of the 'Red Queen' (running to stay in place) evolutionary dynamics.
Frost SD, Wrin T, Smith DM, Kosakovsky Pond SL, Liu Y, Paxinos E, Chappey C, Galovich J, Beauchaine J, Petropoulos CJ, Little SJ, Richman DD. "Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection." Proc Natl Acad Sci USA. 2005 Dec 20;102(51):18514-9.

No comments: