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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.

Original publication

DOI

10.1084/jem.20092060

Type

Journal article

Journal

J Exp Med

Publication Date

18/01/2010

Volume

207

Pages

51 - 59

Keywords

CD8-Positive T-Lymphocytes, Cell Line, Chronic Disease, Cohort Studies, Epitopes, T-Lymphocyte, Evolution, Molecular, Female, Gene Products, gag, Genes, MHC Class I, HIV Infections, HIV-1, Humans, Male, Polymorphism, Genetic, RNA, Antisense, RNA, Viral, South Africa, Transcription, Genetic, nef Gene Products, Human Immunodeficiency Virus, pol Gene Products, Human Immunodeficiency Virus