Document Detail


Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4(+) T cell depletion.
MedLine Citation:
PMID:  23140171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8(+) T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8(+) T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry. The autologous HIV gag sequences were obtained. We demonstrate that patients targeting a conserved HIV-Gag-epitope in early infection maintained their epitope-specific CD8(+) T cell response throughout the study period. Patients targeting a variable epitope showed decreased immune responses over time, although there was no limitation of the functional profile, and they were likely to target additional variable epitopes. Maintained immune responses to conserved epitopes were associated with no or limited sequence evolution within the targeted epitope. Patients with immune responses targeting conserved epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log(10) difference). Furthermore, the rate of CD4(+) T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1.85% per month). Previous studies have shown that targeting of antigens based on specific HLA types is associated with a better disease course. In this study we show that categorizing epitopes based on their variability is associated with clinical outcome.
Authors:
Carina L Perez; Jeffrey M Milush; Marcus Buggert; Emily M Eriksson; Mette V Larsen; Teri Liegler; Wendy Hartogensis; Peter Bacchetti; Ole Lund; Frederick M Hecht; Douglas F Nixon; Annika C Karlsson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-08
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  29     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-08-02     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  602-12     Citation Subset:  IM; X    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/JF905572;  JF905573;  JF905574;  JF905575;  JF905576;  JF905577;  JF905578;  JF905579;  JF905580;  JF905581;  JF905582;  JF905583;  JF905584;  JF905585;  JF905586;  JF905587;  JF905588;  JF905589;  JF905590;  JF905591;  JF905592;  JF905593;  JF905594
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MeSH Terms
Descriptor/Qualifier:
CD8-Positive T-Lymphocytes / immunology*
Cohort Studies
Disease Progression
Epitopes / genetics,  immunology
Flow Cytometry
HIV / genetics,  immunology*,  isolation & purification
HIV Infections / immunology*,  pathology,  virology*
Humans
Molecular Sequence Data
Plasma / virology
RNA, Viral / genetics
San Francisco
Sequence Analysis, DNA
Viral Load*
gag Gene Products, Human Immunodeficiency Virus / genetics,  immunology*
Grant Support
ID/Acronym/Agency:
K24 AT007827/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/Epitopes; 0/RNA, Viral; 0/gag Gene Products, Human Immunodeficiency Virus
Comments/Corrections

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