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Pathogenesis and Immunity

Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors

Justin R. Bailey, Timothy P. Brennan, Karen A. O'Connell, Robert F. Siliciano, Joel N. Blankson
Justin R. Bailey
1Department of Medicine, Johns Hopkins University School of Medicine
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Timothy P. Brennan
1Department of Medicine, Johns Hopkins University School of Medicine
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Karen A. O'Connell
1Department of Medicine, Johns Hopkins University School of Medicine
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Robert F. Siliciano
1Department of Medicine, Johns Hopkins University School of Medicine
2the Howard Hughes Medical Institute, Baltimore, Maryland 21205
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Joel N. Blankson
1Department of Medicine, Johns Hopkins University School of Medicine
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  • For correspondence: jblanks@jhmi.edu
DOI: 10.1128/JVI.01958-08
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ABSTRACT

Elite suppressors (ES) are human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml without treatment. The observation that the HLA-B*57 allele is overrepresented in these patients implies that HIV-1-specific CD8+ T cells play a key role in suppressing viral replication. We have previously shown that while CD8+ T-cell escape mutations are rarely seen in proviral Gag sequences in resting CD4+ T cells from peripheral blood, they are present in every clone amplified from the low levels of free virus in the plasma of HLA-B*57+ ES. In this study, we compared the pattern of mutations in Nef sequences amplified from peripheral blood CD4+ T cells and from plasma virus. We show that Nef mutations are present in plasma virus but are rare in the cellular sequences and provide evidence that these plasma Nef variants represent novel escape mutants. The results provide further evidence of CD8+ T-cell-mediated selective pressure on plasma virus in ES and suggest that there must be ongoing HIV-1 replication in spite of the very low viral loads seen for these patients.

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Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors
Justin R. Bailey, Timothy P. Brennan, Karen A. O'Connell, Robert F. Siliciano, Joel N. Blankson
Journal of Virology Dec 2008, 83 (1) 88-97; DOI: 10.1128/JVI.01958-08

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Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors
Justin R. Bailey, Timothy P. Brennan, Karen A. O'Connell, Robert F. Siliciano, Joel N. Blankson
Journal of Virology Dec 2008, 83 (1) 88-97; DOI: 10.1128/JVI.01958-08
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KEYWORDS

CD8-Positive T-Lymphocytes
HIV Infections
HIV Long-Term Survivors
HIV-1
HLA-B Antigens
Selection, Genetic
nef Gene Products, Human Immunodeficiency Virus

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