Transmission of human immunodeficiency virus type 1 from a patient who developed AIDS to an elite suppressor

Justin R. Bailey, Karen O'Connell, Hung Chih Yang, Yefei Han, Jie Xu, Benjamin Jilek, Thomas M. Williams, Stuart C. Ray, Robert F. Siliciano, Joel N. Blankson

Research output: Contribution to journalArticlepeer-review

Abstract

Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml. The mechanisms involved in this control of viral replication remain unclear. Prior studies suggested that these patients, as well as long-term nonprogressors, are infected with defective HIV-1 variants. Other reports have shown that the HLA-B*27 and -B*57 alleles are overrepresented in these patients, suggesting that host factors play a role in the control of viral replication. In order to distinguish between these hypotheses, we studied differences in viral isolates and immune responses of an HIV-1 transmission pair. While both patients are HLA-B*57 positive, the transmitter progressed to AIDS, whereas the recipient, who is also HLA-B*27 positive, is an ES. Isolates from both patients were replication competent and contained the T242N escape mutation in Gag, which is known to decrease viral fitness. While the acquisition of compensatory mutations occurred in isolates from the progressor, a superior HIV-specific CD8+ T-cell response in the ES appears to have prevented viral replication and thus the evolution toward a more fit variant. In addition, CD8+ T cells in the ES have selected for a rare mutation in an immunodominant HLA-B*27-restricted Gag epitope, which also has a negative impact on fitness. The results strongly suggest that through direct and indirect mechanisms, CD8+ T cells in some ES control HIV-1 isolates are capable of causing profound immunosuppression.

Original languageEnglish (US)
Pages (from-to)7395-7410
Number of pages16
JournalJournal of virology
Volume82
Issue number15
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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