Transmission of Human Immunodeficiency Virus Type 1 from a Patient Who Developed AIDS to an Elite Suppressor

Author:

Bailey Justin R.1,O'Connell Karen1,Yang Hung-Chih1,Han Yefei1,Xu Jie1,Jilek Benjamin1,Williams Thomas M.2,Ray Stuart C.1,Siliciano Robert F.13,Blankson Joel N.1

Affiliation:

1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

2. Department of Pathology, University of New Mexico School of Medicine and Tricore Reference Laboratories, Albuquerque, New Mexico 87131

3. Howard Hughes Medical Institute, Chevy Chase, Maryland

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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