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Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses

Authors
 Jonathan R. Honegger  ;  Seungtaek Kim  ;  Aryn A. Price  ;  Jennifer A. Kohout  ;  Kevin L. McKnight  ;  Mona R. Prasad  ;  Stanley M. Lemon  ;  Arash Grakoui  ;  Christopher M. Walker 
Citation
 NATURE MEDICINE, Vol.19(11) : 1529-1533, 2013 
Journal Title
NATURE MEDICINE
ISSN
 1078-8956 
Issue Date
2013
MeSH
Adult ; Amino Acid Sequence ; Amino Acid Substitution ; Female ; Genes, MHC Class I* ; HLA-B Antigens/genetics ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications* ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/immunology* ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Molecular Sequence Data ; Mutation* ; Parturition/immunology ; Postpartum Period/genetics ; Postpartum Period/immunology ; Pregnancy ; Pregnancy Complications, Infectious/genetics ; Pregnancy Complications, Infectious/immunology* ; Pregnancy Complications, Infectious/virology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/virology ; Viremia/complications ; Viremia/genetics ; Viremia/immunology
Keywords
Adult ; Amino Acid Sequence ; Amino Acid Substitution ; Female ; Genes, MHC Class I* ; HLA-B Antigens/genetics ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications* ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/immunology* ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Molecular Sequence Data ; Mutation* ; Parturition/immunology ; Postpartum Period/genetics ; Postpartum Period/immunology ; Pregnancy ; Pregnancy Complications, Infectious/genetics ; Pregnancy Complications, Infectious/immunology* ; Pregnancy Complications, Infectious/virology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/virology ; Viremia/complications ; Viremia/genetics ; Viremia/immunology
Abstract
Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV)1. Vertical transmission occurs in 3–5% of cases2 and accounts for most new childhood HCV infections1,3. HCV-specific CD8+ cytotoxic T-lymphocytes (CTLs) play a vital role in the clearance of acute infections4–6, but in the 60–80% of infections that persist these cells become functionally exhausted or select mutant viruses that escape T-cell recognition7–9. Increased HCV replication during pregnancy10,11 suggests that maternofetal immune tolerance mechanisms12 may further impair HCV-specific CTLs, limiting their selection pressure on persistent viruses. To assess this possibility, we characterized the circulating viral quasispecies during and after consecutive pregnancies. This revealed a loss of some escape mutations in class I epitopes in pregnancy associated with emergence of more fit viruses13. CTL selection pressure was reimposed after childbirth, when escape mutations in these epitopes again predominated in the quasispecies and viral load dropped sharply14. Importantly, viruses transmitted perinatally were those with enhanced fitness due to reversion of escape mutations. Our findings indicate that immunoregulatory changes of pregnancy reduce CTL selection pressure on HCV class I epitopes, thereby facilitating vertical transmission of viruses with optimized replicative fitness.
Files in This Item:
T201305407.pdf Download
DOI
10.1038/nm.3351
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Seung Taek(김승택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88980
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