HIV suppression maintained in HLA-B*57+ elite suppressors despite CTL escape mutations
Viral suppression is maintained in HIV-1-infected HLA-B*57+ elite suppressors despite cytotoxic T lymphocyte escape mutations.
According to a study from the United States, “Rare human immunodeficiency virus 1-infected individuals, termed elite suppressors (ES), maintain plasma virus levels of <50 copies/mL and normal CD4 counts without therapy.
“The major histocompatibility complex class I allele group human histocompatibility leukocyte antigen (HLA)-B*57 is over-represented in this population. Mutations in HLA-B*57 restricted epitopes have been observed in ES, but their significance has remained unclear.”
“Here we investigate the extent and impact of cytotoxic T lymphocyte (CTL) escape mutations in HLA-B*57+ ES. We provide the first direct evidence that most ES experience chronic low level viremia,” J.R. Bailey and colleagues at Johns Hopkins University reported.
“Sequencing revealed a striking discordance between the genotypes of plasma virus and archived provirus in resting CD4+ T cells. Mutations in HLAB* 57-restricted Gag epitopes were present in all viruses from plasma but were rare in proviruses, suggesting powerful selective pressure acting at these epitopes.
“Surprisingly,” said the authors, “strong CD8+ T cell interferon-gamma responses were detected against some mutant epitopes found in plasma virus, suggesting the development of de novo responses to viral variants. In some individuals, relative CD8+ T cell interleukin-2 responses showed better correlation with the selection observed in vivo.”
Scientists concluded, “Thus, analysis of low level viremia reveals an unexpectedly high level of CTL escape mutations reflecting selective pressure acting at HLA-B*57 restricted epitopes in ES. Continued viral suppression probably reflects CTL responses against unmutated epitopes and residual or de novo responses against epitopes with escape mutations.”
Bailey and colleagues published the results of their research in the Journal of Experimental Medicine (Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. J Exp Med, 2006;203(5):1357-1369).
For additional information, contact J.N. Blankson, Johns Hopkins University, School Medical, Dept. of Medical, Baltimore, MD 21287, USA.
The publisher of the Journal of Experimental Medicine can be contacted at: Rockefeller University Press, 1114 First Avenue, 4TH FL, New York, NY 10021, USA.
Revision date: June 21, 2011
Last revised: by David A. Scott, M.D.