期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 207, 期 1, 页码 51-59出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20092060
关键词
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资金
- National Institutes of Health (NIH) [R21 AI 73103, R01 AI 084772, AI 64060, P30 AI 050409]
- Bill and Melinda Gates Foundation [37874]
- University of Alabama at Birmingham-Centers for AIDS Research [P30 AI 027767]
- Microsoft Research Corporation
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.
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