PMID- 28594230
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20181202
IS  - 1931-8405 (Electronic)
IS  - 0889-2229 (Print)
IS  - 0889-2229 (Linking)
VI  - 33
IP  - 8
DP  - 2017 Aug
TI  - Conserved HIV-1 Gag p24 Epitopes Elicit Cellular Immune Responses That Impact 
      Disease Outcome.
PG  - 832-842
LID - 10.1089/AID.2016.0168 [doi]
AB  - Although the breadth of the human immunodeficiency virus type 1 (HIV-1)-specific 
      cellular immune response and its impact on the control of viral replication have 
      already been addressed, reported data have proven controversial. We hypothesize 
      that the nature of targeted epitopes, rather than the simple breadth or magnitude 
      of responses, correlates with disease outcome. In this study, we explore the 
      occurrence of patterns of Gag p24 recognition among untreated HIV-1-infected 
      patients by identifying the epitopes that compose such patterns and how they 
      distinctly associate with disease progression. Utilizing enzyme-linked immunospot 
      (ELISPOT) interferon gamma (IFN-gamma), we screened cellular responses of 27 
      HIV-1-infected subjects against 15-mer peptides encompassing the whole Gag p24 
      protein. Obtained data were used to develop a clustering analysis that allowed 
      definition of two groups of individuals with totally distinct patterns of 
      recognition. Although targeted Gag p24 peptides were completely different between 
      the two groups, the breadth and magnitude of the responses were not. 
      Interestingly, viral control and preservation of CD4(+) T cells were increased in 
      one group. In addition, we compared genetic conservation of amino acid sequences 
      of the recognized peptides, as well as of the human leucocyte antigen class I 
      (HLA-I)-restricted epitopes within them. Subjects presenting higher control of 
      HIV-1 replication targeted more conserved epitopes, and higher genetic variation 
      was present mainly in anchor residues for HLA-I molecules. We strengthen the 
      existing evidence from cases of HIV-1 infection in humans that, cellular immune 
      responses targeting conserved epitopes, rather than the magnitude and breadth of 
      responses, associate with a better control of viral replication and maintenance 
      of peripheral CD4(+) T cell counts.
FAU - Tarosso, Leandro F
AU  - Tarosso LF
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
FAU - Vieira, Vinicius A
AU  - Vieira VA
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
FAU - Sauer, Mariana M
AU  - Sauer MM
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
FAU - Tomiyama, Helena I
AU  - Tomiyama HI
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
FAU - Kalil, Jorge
AU  - Kalil J
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
FAU - Kallas, Esper G
AU  - Kallas EG
AD  - Division of Clinical Immunology and Allergy, University of Sao Paulo School of 
      Medicine, Sao Paulo, Brazil .
LA  - eng
PT  - Journal Article
DEP - 20170803
PL  - United States
TA  - AIDS Res Hum Retroviruses
JT  - AIDS research and human retroviruses
JID - 8709376
RN  - 0 (Epitopes)
RN  - 0 (HIV Core Protein p24)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Cohort Studies
MH  - Conserved Sequence
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitopes/genetics/*immunology
MH  - Female
MH  - HIV Core Protein p24/genetics/*immunology
MH  - HIV Infections/*immunology
MH  - HIV-1/genetics/*immunology
MH  - Humans
MH  - *Immunity, Cellular
MH  - Interferon-gamma/metabolism
MH  - Male
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC5564043
OTO - NOTNLM
OT  - Gag
OT  - T cells
OT  - antigen processing and presentation
OT  - immune response
COIS- No competing financial interests exist.
EDAT- 2017/06/09 06:00
MHDA- 2018/04/18 06:00
PMCR- 2018/08/01
CRDT- 2017/06/09 06:00
PHST- 2017/06/09 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/06/09 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 10.1089/aid.2016.0168 [pii]
AID - 10.1089/AID.2016.0168 [doi]
PST - ppublish
SO  - AIDS Res Hum Retroviruses. 2017 Aug;33(8):832-842. doi: 10.1089/AID.2016.0168. 
      Epub 2017 Aug 3.