Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness
Department of Pediatrics; Program in Molecular Medicine; Interdisciplinary Graduate Program
Medical Subject Headings
Amino Acid Sequence; Amino Acid Substitution; CD8-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Female; HIV Antigens; HIV Core Protein p24; HIV Infections; HIV-1; Hela Cells; Humans; Infant; Infectious Disease Transmission, Vertical; Molecular Sequence Data; *Mutation; Sequence Analysis, DNA; Transfection; Virus Replication; gag Gene Products, Human Immunodeficiency; Virus
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Infect Dis. 2008 Jan 15;197(2):300-8. Link to article on publisher's site
The Journal of infectious diseases
Sanchez-Merino, Victor; Farrow, Melissa Ann; Brewster, Frank E.; Somasundaran, Mohan; and Luzuriaga, Katherine, "Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness" (2008). GSBS Student Publications. 1428.