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    Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness

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    Authors
    Sanchez-Merino, Victor
    Farrow, Melissa Ann
    Farrow, Melissa Ann
    Brewster, Frank E.
    Somasundaran, Mohan
    Luzuriaga, Katherine
    Brewster, Frank E.
    Somasundaran, Mohan
    Luzuriaga, Katherine
    UMass Chan Affiliations
    Interdisciplinary Graduate Program
    Program in Molecular Medicine
    Department of Pediatrics
    Document Type
    Journal Article
    Publication Date
    2008-01-08
    Keywords
    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
    
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    Link to Full Text
    http://dx.doi.org/10.1086/524845
    Abstract
    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.
    Source
    J Infect Dis. 2008 Jan 15;197(2):300-8. Link to article on publisher's site
    DOI
    10.1086/524845
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32875
    PubMed ID
    18177249
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1086/524845
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    Morningside Graduate School of Biomedical Sciences Scholarly Publications

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