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Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection

Journal Article · · PLoS Pathogens
 [1];  [2];  [3];  [3];  [4];  [5];  [6];  [6];  [7];  [8];  [9];  [10];  [11];  [11];  [12];  [13];  [14];  [4];  [15];  [3] more »;  [16] « less
  1. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery; DOE/OSTI
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Div.
  3. Univ. of Oxford (United Kingdom). Weatherall Inst. of Molecular Medicine
  4. Univ. of Oxford (United Kingdom). Nuffield Dept. of Clinical Medicine
  5. Univ. of Alabama, Birmingham, AL (United States). Dept. of Microbiology
  6. VID Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  7. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Div.; Baylor Univ., Waco, TX (United States). Dept. of Statistical Sciences
  8. Univ. of Pennsylvania, Philadelphia, PA (United States). School of Medicine. Dept. of Microbiology
  9. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Medicine
  10. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine
  11. Mortimer Market Centre, London (United Kingdom). Centre for Sexual Health & HIV Research
  12. Univ. of North Carolina, Chapel Hill, NC (United States). Medical Center. Dept. of Surgery; Univ. of North Carolina, Chapel Hill, NC (United States). Medical Center. Dept. of Immunology
  13. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine; Univ. of North Carolina, Chapel Hill, NC (United States). Medical Center. Dept. of Immunology
  14. National Inst. for Communicable Diseases, Johannesburg (South Africa). AIDS Research Unit
  15. National Institutes of Health (NIH), Bethesda, MD (United States). Vaccine Research Center
  16. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery; Duke Univ., Durham, NC (United States). Medical Center. Dept. of Immunology
+ Show Author Affiliations

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1b-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1627898
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 2 Vol. 7; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (37)

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Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection journal March 2017
Correction for Anthony et al., “Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope” journal May 2018
Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection journal September 2014
Baseline CD4+ T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression journal September 2014
Structured Observations Reveal Slow HIV-1 CTL Escape journal February 2015
Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV journal June 2018
The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization journal April 2012
Reversion and T Cell Escape Mutations Compensate the Fitness Loss of a CD8+ T Cell Escape Mutant in Their Cognate Transmitted/Founder Virus journal July 2014
Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection journal March 2012
Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection journal August 2016
Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections journal May 2019
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Mechanisms of CD8 + T cell-mediated suppression of HIV/SIV replication journal March 2018
Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection journal October 2016
Inverse statistical physics of protein sequences: a key issues review journal January 2018
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Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment journal April 2013
Analysis of HLA A*02 Association with Vaccine Efficacy in the RV144 HIV-1 Vaccine Trial journal May 2014
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Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection
  • L., Nordstrom, Jeffrey; M., Margolis, David; D., Tomaras, Georgia
  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/5r0x-ga28
text January 2016
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  • Jean-Pierre, Routy,; J., McMichael, Andrew; Sorachai, Nitayaphan,
  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/fh7w-ks33
text January 2016
Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication text January 2012
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Harnessing CD8+ T Cells Under HIV Antiretroviral Therapy journal February 2019
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Temporal Dynamics of the Primary Human T Cell Response to Yellow Fever Virus 17D As It Matures from an Effector- to a Memory-Type Response journal January 2013
Epitope-Specific CD8 + T Cell Kinetics Rather than Viral Variability Determine the Timing of Immune Escape in Simian Immunodeficiency Virus Infection journal March 2015
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Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection text January 2012

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV
HIV-1
T cells
cloning
cytotoxic T cells
entropy
graphs
immune response