RGD Reference Report - Influence of IFNL3 and HLA-DPB1 genotype on postpartum control of hepatitis C virus replication and T-cell recovery. - Rat Genome Database

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Influence of IFNL3 and HLA-DPB1 genotype on postpartum control of hepatitis C virus replication and T-cell recovery.

Authors: Honegger, Jonathan R  Tedesco, Dana  Kohout, Jennifer A  Prasad, Mona R  Price, Aryn A  Lindquist, Tera  Ohmer, Samantha  Moore-Clingenpeel, Melissa  Grakoui, Arash  Walker, Christopher M 
Citation: Honegger JR, etal., Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10684-9. doi: 10.1073/pnas.1602337113. Epub 2016 Sep 6.
RGD ID: 150429796
Pubmed: PMID:27601657   (View Abstract at PubMed)
PMCID: PMC5035892   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1602337113   (Journal Full-text)

Chronic hepatitis C virus (HCV) infection is characterized by exhaustion of virus-specific T-cells and stable viremia. Pregnancy is an exception. Viremia gradually climbs during gestation but sometimes declines sharply in the months following delivery. Here, we demonstrated that postpartum HCV control was associated with enhanced virus-specific T-cell immunity. Women with viral load declines of at least 1 log10 between the third trimester and 3-mo postpartum exhibited HCV-specific T-cell responses of greater breadth (P = 0.0052) and magnitude (P = 0.026) at 3-mo postpartum than women who failed to control viremia. Moreover, viral dynamics were consistent in women after consecutive pregnancies, suggesting genetic underpinnings. We therefore searched for genetic associations with human leukocyte antigen (HLA) alleles and IFN-λ3 gene (IFNL3) polymorphisms that influence HCV infection outcome. Postpartum viral control was associated with the IFNL3 rs12979860 genotype CC (P = 0.045 at 6 mo) that predicts a positive response to IFN-based therapy. Suppression of virus replication after pregnancy was also strongly influenced by the HLA class II DPB1 locus. HLA-DPB1 alleles are classified by high and low patterns of expression. Carriage of at least one high-expression HLA-DPB1 allele predicted resurgent virus-specific T-cell immunity and viral control at 3-mo postpartum (P = 0.0002). When considered together in multivariable analysis, IFNL3 and HLA-DPB1 independently affected viral control at 3- and 6-mo postpartum. Together, these findings support a model where spontaneous control of HCV such as sometimes follows pregnancy is governed by genetic polymorphisms that affect type III IFN signaling and virus-specific cellular immune responses.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HLA-DPB1HumanChronic Hepatitis C amelioratesIAGP DNA:polymorphism: :HLA-DPB1*04:01 (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HLA-DPB1HumanViral hepatitis amelioratesIAGP DNA:polymorphism: :HLA-DPB1*04:01 RGD 
HLA-DPB1HumanViremia amelioratesIAGP DNA:polymorphism: :HLA-DPB1*04:01 RGD 
Objects Annotated

Genes (Homo sapiens)
HLA-DPB1  (major histocompatibility complex, class II, DP beta 1)


Additional Information