Hepatitis C viral variants bear signatures of de novo CD8+ T cell and antibody pressure after spontaneous postpartum viral suppression
8 affiliations
- 1Center for Microbe and Immunity Research, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
- 2Division of Pediatric Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH 43205
- 3Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210
- 4Division of Microbiology and Immunology, Emory National Primate Research Center, Emory Vaccine Center, Atlanta, GA 30307
- 5Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
- 6Department of Obstetrics and Gynecology, College of Medicine, The Ohio State University, Columbus, OH 43210
- 7Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210
- 8Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30307
Abstract
Progression to chronic hepatitis C virus (HCV) infection entails loss of HCV-specific CD4+ T cell help, emergence of viral variants that escape recognition by CD8+ T cells and neutralizing antibodies, and exhaustion of CD8+ T cells targeting remaining intact epitopes. Once chronic infection has been established, it is generally lifelong without treatment. However, in some chronically infected women, a surprising postpartum viral load decline has been linked to resurgent functional HCV-specific CD4+ helper T cells. A minority of women even spontaneously clear long-standing chronic infection postpartum. To test whether restored T cell help boosts HCV-specific CD8+ T cell or antibody responses in women with postpartum viral control, we performed serial near-full-length deep sequencing of HCV genomes to assess evolution of viral MHC class I epitopes and antibody epitopes in nine women with significant postpartum viral declines (≥ 1 log10 at 3 mo postpartum, “controllers”) and 12 with more stable levels (“noncontrollers”). Although not associated with mutations arising early postpartum, at 12 to 24 mo postpartum, viral control was strongly associated with amino acid mutations in epitopes predicted to be targeted by CD8+ T cells and neutralizing antibodies. Plasma from controllers also demonstrated a postpartum increase in neutralization of multiple HCV strains. Together, these findings support the hypothesis that postpartum viral control is mediated by CD8+ T cell and antibody pressure.
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BibTeX
@article{phelps2026hepatitis,
title = {{Hepatitis C viral variants bear signatures of de novo CD8+ T cell and antibody pressure after spontaneous postpartum viral suppression}},
author = {Christopher C. Phelps and Stephanie Smith and John Gridley and Jennifer A. Kohout and Zhaohui Xu and Joseph Marcotrigiano and Kara Rood and Nicole E. Skinner and Arash Grakoui and Jonathan R. Honegger and Christopher M. Walker},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2610110123},
url = {https://doi.org/10.1073/pnas.2610110123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Hepatitis C viral variants bear signatures of de novo CD8+ T cell and antibody pressure after spontaneous postpartum viral suppression
AU - Christopher C. Phelps
AU - Stephanie Smith
AU - John Gridley
AU - Jennifer A. Kohout
AU - Zhaohui Xu
AU - Joseph Marcotrigiano
AU - Kara Rood
AU - Nicole E. Skinner
AU - Arash Grakoui
AU - Jonathan R. Honegger
AU - Christopher M. Walker
PY - 2026
DA - 2026/10/27
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2610110123
UR - https://doi.org/10.1073/pnas.2610110123
AB - Progression to chronic hepatitis C virus (HCV) infection entails loss of HCV-specific CD4+ T cell help, emergence of viral variants that escape recognition by CD8+ T cells and neutralizing antibodies, and exhaustion of CD8+ T cells targeting remaining intact epitopes. Once chronic infection has been established, it is generally lifelong without treatment. However, in some chronically infected women, a surprising postpartum viral load decline has been linked to resurgent functional HCV-specific CD4+ helper T cells. A minority of women even spontaneously clear long-standing chronic infection postpartum. To test whether restored T cell help boosts HCV-specific CD8+ T cell or antibody responses in women with postpartum viral control, we performed serial near-full-length deep sequencing of HCV genomes to assess evolution of viral MHC class I epitopes and antibody epitopes in nine women with significant postpartum viral declines (≥ 1 log10 at 3 mo postpartum, “controllers”) and 12 with more stable levels (“noncontrollers”). Although not associated with mutations arising early postpartum, at 12 to 24 mo postpartum, viral control was strongly associated with amino acid mutations in epitopes predicted to be targeted by CD8+ T cells and neutralizing antibodies. Plasma from controllers also demonstrated a postpartum increase in neutralization of multiple HCV strains. Together, these findings support the hypothesis that postpartum viral control is mediated by CD8+ T cell and antibody pressure.
SN - 0027-8424
SN - 1091-6490
ER -