Control of HIV-1 in elite suppressors despite ongoing replication and evolution in plasma virus

Karen A. O'Connell, Timothy P. Brennan, Justin Bailey, Stuart Campbell Ray, Robert F Siliciano, Joel N Blankson

Research output: Contribution to journalArticle

Abstract

A subset of HIV-1-infected patients known as elite controllers or suppressors (ES) control the virus naturally. We have previously demonstrated sequence discordance between proviral and plasma gag clones in ES, much of which can be attributed to selective pressure from the host (J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, J. Exp. Med. 203:1357-1369, 2006). However, it is not clear whether ongoing viral replication continues in ES once the control of viremia has been established or whether selective pressure impacts this evolution. The cytotoxic T-lymphocyte (CTL) response in ES often targets Gag and frequently is superior to that of HIV-1 progressors, partially due to the HLA class I alleles B*57/5801 and B*27, which are overrepresented in ES. We therefore examined longitudinal plasma and proviral gag sequences from HLA-B*57/5801 and -B*27 ES. Despite the highly conserved nature of gag, we observed clear evidence of evolution in the plasma virus, largely due to synonymous substitutions. In contrast, evolution was rare in proviral clones, suggesting that ongoing replication in ES does not permit the significant reseeding of the latent reservoir. Interestingly, there was little continual evolution in CTL epitopes, and we detected de novo CTL responses to autologous viral mutants. Thus, some ES control viremia despite ongoing replication and evolution.

Original languageEnglish (US)
Pages (from-to)7018-7028
Number of pages11
JournalJournal of Virology
Volume84
Issue number14
DOIs
StatePublished - Jul 2010

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Cytotoxic T-Lymphocytes
Human immunodeficiency virus 1
HIV-1
Viremia
cytotoxic T-lymphocytes
Viruses
viruses
Clone Cells
viremia
T-Lymphocyte Epitopes
clones
Alleles
virus replication
epitopes
HIV long-term survivors
alleles
mutants

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Control of HIV-1 in elite suppressors despite ongoing replication and evolution in plasma virus. / O'Connell, Karen A.; Brennan, Timothy P.; Bailey, Justin; Ray, Stuart Campbell; Siliciano, Robert F; Blankson, Joel N.

In: Journal of Virology, Vol. 84, No. 14, 07.2010, p. 7018-7028.

Research output: Contribution to journalArticle

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