Journal article
CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription
The Journal of experimental medicine, Vol.207(1), pp.51-59
01/18/2010
DOI: 10.1084/jem.20092060
PMCID: PMC2812545
PMID: 20065064
Abstract
Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1
gag
,
pol
, and
nef
genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity.
Details
- Title: Subtitle
- CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription
- Creators
- Anju Bansal - University of Alabama at BirminghamJonathan Carlson - MicrosoftJiyu Yan - University of Alabama at BirminghamOlusimidele T. Akinsiku - University of Alabama at BirminghamMalinda Schaefer - Emory UniversitySteffanie Sabbaj - University of Alabama at BirminghamAnne Bet - University of Alabama at BirminghamDavid N. Levy - New York UniversitySonya Heath - University of Alabama at BirminghamJianming Tang - University of Alabama at BirminghamRichard A. Kaslow - University of Alabama at BirminghamBruce D. Walker - Ragon Institute of MGH, MIT and HarvardThumbi Ndung’u - University of KwaZulu-NatalPhilip J. Goulder - Ragon Institute of MGH, MIT and HarvardDavid Heckerman - MicrosoftEric Hunter - Emory UniversityPaul A. Goepfert - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.207(1), pp.51-59
- Publisher
- The Rockefeller University Press
- DOI
- 10.1084/jem.20092060
- PMID
- 20065064
- PMCID
- PMC2812545
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Alternative title
- Antisense HIV-1–specific CD8 T cell epitopes
- Language
- English
- Date published
- 01/18/2010
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984697043802771
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