CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription

Anju Bansal, Jonathan Carlson, Jiyu Yan, Olusimidele T. Akinsiku, Malinda Schaefer, Steffanie Sabbaj, Anne Bet, David Levy, Sonya Heath, Jianming Tang, Richard A. Kaslow, Bruce D. Walker, Thumbi Ndung'u, Philip J. Goulder, David Heckerman, Eric Hunter, Paul A. Goepfert

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Experimental Medicine
Volume207
Issue number1
DOIs
StatePublished - Jan 18 2010

Fingerprint

HIV-1
Epitopes
T-Lymphocytes
Pressure
Reading Frames
Infection
nef Genes
Active Immunity
Genome
pol Genes
gag Genes
Retroviridae
HLA Antigens
Open Reading Frames
Genes
Antiviral Agents
Immunity
Proteins
Vaccines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Bansal, A., Carlson, J., Yan, J., Akinsiku, O. T., Schaefer, M., Sabbaj, S., ... Goepfert, P. A. (2010). CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription. Journal of Experimental Medicine, 207(1), 51-59. https://doi.org/10.1084/jem.20092060

CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription. / Bansal, Anju; Carlson, Jonathan; Yan, Jiyu; Akinsiku, Olusimidele T.; Schaefer, Malinda; Sabbaj, Steffanie; Bet, Anne; Levy, David; Heath, Sonya; Tang, Jianming; Kaslow, Richard A.; Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J.; Heckerman, David; Hunter, Eric; Goepfert, Paul A.

In: Journal of Experimental Medicine, Vol. 207, No. 1, 18.01.2010, p. 51-59.

Research output: Contribution to journalArticle

Bansal, A, Carlson, J, Yan, J, Akinsiku, OT, Schaefer, M, Sabbaj, S, Bet, A, Levy, D, Heath, S, Tang, J, Kaslow, RA, Walker, BD, Ndung'u, T, Goulder, PJ, Heckerman, D, Hunter, E & Goepfert, PA 2010, 'CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription', Journal of Experimental Medicine, vol. 207, no. 1, pp. 51-59. https://doi.org/10.1084/jem.20092060
Bansal, Anju ; Carlson, Jonathan ; Yan, Jiyu ; Akinsiku, Olusimidele T. ; Schaefer, Malinda ; Sabbaj, Steffanie ; Bet, Anne ; Levy, David ; Heath, Sonya ; Tang, Jianming ; Kaslow, Richard A. ; Walker, Bruce D. ; Ndung'u, Thumbi ; Goulder, Philip J. ; Heckerman, David ; Hunter, Eric ; Goepfert, Paul A. / CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 1. pp. 51-59.
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