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

DC Field Value Language
dc.contributor.author김승택-
dc.date.accessioned2014-12-18T09:52:07Z-
dc.date.available2014-12-18T09:52:07Z-
dc.date.issued2013-
dc.identifier.issn1078-8956-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88980-
dc.description.abstractGlobally, 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.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfNATURE MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdult-
dc.subject.MESHAmino Acid Sequence-
dc.subject.MESHAmino Acid Substitution-
dc.subject.MESHFemale-
dc.subject.MESHGenes, MHC Class I*-
dc.subject.MESHHLA-B Antigens/genetics-
dc.subject.MESHHepacivirus/genetics-
dc.subject.MESHHepatitis C, Chronic/complications*-
dc.subject.MESHHepatitis C, Chronic/genetics-
dc.subject.MESHHepatitis C, Chronic/immunology*-
dc.subject.MESHHumans-
dc.subject.MESHInfant-
dc.subject.MESHInfant, Newborn-
dc.subject.MESHInfectious Disease Transmission, Vertical-
dc.subject.MESHMolecular Sequence Data-
dc.subject.MESHMutation*-
dc.subject.MESHParturition/immunology-
dc.subject.MESHPostpartum Period/genetics-
dc.subject.MESHPostpartum Period/immunology-
dc.subject.MESHPregnancy-
dc.subject.MESHPregnancy Complications, Infectious/genetics-
dc.subject.MESHPregnancy Complications, Infectious/immunology*-
dc.subject.MESHPregnancy Complications, Infectious/virology-
dc.subject.MESHT-Lymphocytes, Cytotoxic/immunology-
dc.subject.MESHT-Lymphocytes, Cytotoxic/virology-
dc.subject.MESHViremia/complications-
dc.subject.MESHViremia/genetics-
dc.subject.MESHViremia/immunology-
dc.titleLoss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Life Science (의생명과학부)-
dc.contributor.googleauthorJonathan R. Honegger-
dc.contributor.googleauthorSeungtaek Kim-
dc.contributor.googleauthorAryn A. Price-
dc.contributor.googleauthorJennifer A. Kohout-
dc.contributor.googleauthorKevin L. McKnight-
dc.contributor.googleauthorMona R. Prasad-
dc.contributor.googleauthorStanley M. Lemon-
dc.contributor.googleauthorArash Grakoui-
dc.contributor.googleauthorChristopher M. Walker-
dc.identifier.doi10.1038/nm.3351-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00661-
dc.relation.journalcodeJ02296-
dc.identifier.eissn1546-170X-
dc.identifier.pmid24162814-
dc.subject.keywordAdult-
dc.subject.keywordAmino Acid Sequence-
dc.subject.keywordAmino Acid Substitution-
dc.subject.keywordFemale-
dc.subject.keywordGenes, MHC Class I*-
dc.subject.keywordHLA-B Antigens/genetics-
dc.subject.keywordHepacivirus/genetics-
dc.subject.keywordHepatitis C, Chronic/complications*-
dc.subject.keywordHepatitis C, Chronic/genetics-
dc.subject.keywordHepatitis C, Chronic/immunology*-
dc.subject.keywordHumans-
dc.subject.keywordInfant-
dc.subject.keywordInfant, Newborn-
dc.subject.keywordInfectious Disease Transmission, Vertical-
dc.subject.keywordMolecular Sequence Data-
dc.subject.keywordMutation*-
dc.subject.keywordParturition/immunology-
dc.subject.keywordPostpartum Period/genetics-
dc.subject.keywordPostpartum Period/immunology-
dc.subject.keywordPregnancy-
dc.subject.keywordPregnancy Complications, Infectious/genetics-
dc.subject.keywordPregnancy Complications, Infectious/immunology*-
dc.subject.keywordPregnancy Complications, Infectious/virology-
dc.subject.keywordT-Lymphocytes, Cytotoxic/immunology-
dc.subject.keywordT-Lymphocytes, Cytotoxic/virology-
dc.subject.keywordViremia/complications-
dc.subject.keywordViremia/genetics-
dc.subject.keywordViremia/immunology-
dc.contributor.alternativeNameKim, Seung Taek-
dc.contributor.affiliatedAuthorKim, Seung Taek-
dc.rights.accessRightsfree-
dc.citation.volume19-
dc.citation.number11-
dc.citation.startPage1529-
dc.citation.endPage1533-
dc.identifier.bibliographicCitationNATURE MEDICINE, Vol.19(11) : 1529-1533, 2013-
dc.identifier.rimsid33719-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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