Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness.
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.
Sanchez-Merino
Victor
V
Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Farrow
Melissa A
MA
Brewster
Frank
F
Somasundaran
Mohan
M
Luzuriaga
Katherine
K
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005260:Female; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D014162:Transfection; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D016655:HIV Core Protein p24; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1