Identification and Characterization of HIV‐1 CD8+ T Cell Escape Variants with Impaired Fitness
1Department of Pediatrics and Program in Molecular Medicine and 2Interdisciplinary Graduate Program, University of Massachusetts Medical School, Worcester
In this study, amino acid sequence variation in human immunodeficiency virus (HIV)–1 Gag CD8+ T cell epitopes was examined in untreated mother‐infant pairs. Several HIV‐1 CD8+ T cell escape variants were identified within maternal plasma viral p17 and p24 sequences that were either not detected or did not persist in the plasma of their non–HLA‐matched HIV‐1–infected infants. Viruses constructed with each of these mutations demonstrated reduced viral replication in vitro and reduced expression of p17 and p24 proteins compared with wild type. Reduced recognition of the variant sequences compared with wild‐type sequence was also demonstrated by enzyme‐linked immunospot assays. Nontransmission or reversion after transmission was thus associated with reduced viral fitness cost in vivo. Better understanding of the balance between CD8+ T cell selective pressures and viral fitness cost may facilitate the identification of optimal viral sequences for inclusion in HIV‐1 vaccines.
Received 9 March 2007; accepted 31 July 2007; electronically published 4 January 2008.
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Online publication date: 1-May-2009.
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Potential conflicts of interest: none reported.
Presented in part: Keystone Symposium, Keystone, Colorado, 27 March–2 April 2006.
Financial support: National Institutes of Health (grants AI 32391 and HD 01489 to K.L.); University of Massachusetts Center for AIDS Research (grant AI 42845).
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Present affiliation: College of the Holy Cross, Worcester, Massachusetts.