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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription
Journal of Experimental Medicine, Volume 207, No. 1, Year 2010
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Description
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. © 2010 Bansal et al.
Authors & Co-Authors
Bansal, Anju
United States, Birmingham
The University of Alabama at Birmingham
Carlson, Jonathan M.
United States, Redmond
Microsoft Research
Yan, Jiyu
United States, Birmingham
The University of Alabama at Birmingham
Akinsiku, Olusimidele T.
United States, Birmingham
The University of Alabama at Birmingham
Schaefer, Malinda R.
United States, Atlanta
Emory University
Sabbaj, Steffanie
United States, Birmingham
The University of Alabama at Birmingham
Bet, Anne
United States, Birmingham
The University of Alabama at Birmingham
Levy, David N.
United States, New York
Nyu College of Dentistry
Heath, Sonya
United States, Birmingham
The University of Alabama at Birmingham
Tang, Jianming
United States, Birmingham
The University of Alabama at Birmingham
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
Walker, Bruce D.
United States, Cambridge
Massachusetts Institute of Technology
South Africa, Durban
University of Kwazulu-natal
Ndung'u, Thumbi P.
United States, Cambridge
Massachusetts Institute of Technology
South Africa, Durban
University of Kwazulu-natal
Goulder, Philip Jeremy Renshaw
United States, Cambridge
Massachusetts Institute of Technology
South Africa, Durban
University of Kwazulu-natal
United Kingdom, Oxford
University of Oxford
Heckerman, David E.
United States, Redmond
Microsoft Research
Hunter, Eric
United States, Atlanta
Emory University
Goepfert, Paul A.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 80
Authors: 17
Affiliations: 7
Identifiers
Doi:
10.1084/jem.20092060
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Infectious Diseases
Study Design
Cohort Study