PMID- 20065065
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20211020
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 207
IP  - 1
DP  - 2010 Jan 18
TI  - Viral adaptation to immune selection pressure by HLA class I-restricted CTL 
      responses targeting epitopes in HIV frameshift sequences.
PG  - 61-75
LID - 10.1084/jem.20091808 [doi]
AB  - CD8+ cytotoxic T lymphocyte (CTL)-mediated immune responses to HIV contribute to 
      viral control in vivo. Epitopes encoded by alternative reading frame (ARF) 
      peptides may be targeted by CTLs as well, but their frequency and in vivo 
      relevance are unknown. Using host genetic (human leukocyte antigen [HLA]) and 
      plasma viral sequence information from 765 HIV-infected subjects, we identified 
      64 statistically significant (q<0.2) associations between specific HLA alleles 
      and sequence polymorphisms in alternate reading frames of gag, pol, and nef that 
      did not affect the regular frame protein sequence. Peptides spanning the top 20 
      HLA-associated imprints were used to test for ex vivo immune responses in 85 
      HIV-infected subjects and showed responses to 10 of these ARF peptides. The most 
      frequent response recognized an HLA-A*03-restricted +2 frame-encoded epitope 
      containing a unique A*03-associated polymorphism at position 6. Epitope-specific 
      CTLs efficiently inhibited viral replication in vitro when viruses containing the 
      wild-type sequence but not the observed polymorphism were tested. Mutating 
      alternative internal start codons abrogated the CTL-mediated inhibition of viral 
      replication. These data indicate that responses to ARF-encoded HIV epitopes are 
      induced during natural infection, can contribute to viral control in vivo, and 
      drive viral evolution on a population level.
FAU - Berger, Christoph T
AU  - Berger CT
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology, Boston, MA 02129, USA.
FAU - Carlson, Jonathan M
AU  - Carlson JM
FAU - Brumme, Chanson J
AU  - Brumme CJ
FAU - Hartman, Kari L
AU  - Hartman KL
FAU - Brumme, Zabrina L
AU  - Brumme ZL
FAU - Henry, Leah M
AU  - Henry LM
FAU - Rosato, Pamela C
AU  - Rosato PC
FAU - Piechocka-Trocha, Alicja
AU  - Piechocka-Trocha A
FAU - Brockman, Mark A
AU  - Brockman MA
FAU - Harrigan, P Richard
AU  - Harrigan PR
FAU - Heckerman, David
AU  - Heckerman D
FAU - Kaufmann, Daniel E
AU  - Kaufmann DE
FAU - Brander, Christian
AU  - Brander C
LA  - eng
GR  - R01 AI067077/AI/NIAID NIH HHS/United States
GR  - R01 A1-067077/PHS HHS/United States
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100111
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Codon, Initiator)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*03 antigen)
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology/virology
MH  - Codon, Initiator/genetics/immunology
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - *Evolution, Molecular
MH  - Female
MH  - Frameshift Mutation/immunology
MH  - HIV/genetics/*immunology
MH  - HIV Infections/genetics/*immunology
MH  - HLA-A Antigens/genetics/*immunology
MH  - HLA-A3 Antigen
MH  - Humans
MH  - Immunity, Cellular/genetics
MH  - Male
MH  - Peptides/genetics/*immunology
MH  - Polymorphism, Genetic/immunology
MH  - Viral Proteins/genetics/*immunology
MH  - Virus Replication/genetics/immunology
PMC - PMC2812535
EDAT- 2010/01/13 06:00
MHDA- 2010/02/18 06:00
PMCR- 2010/07/18
CRDT- 2010/01/13 06:00
PHST- 2010/01/13 06:00 [entrez]
PHST- 2010/01/13 06:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
PHST- 2010/07/18 00:00 [pmc-release]
AID - jem.20091808 [pii]
AID - 20091808 [pii]
AID - 10.1084/jem.20091808 [doi]
PST - ppublish
SO  - J Exp Med. 2010 Jan 18;207(1):61-75. doi: 10.1084/jem.20091808. Epub 2010 Jan 11.