Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees

Babs E Verstrepen,Harry L A Janssen,Petra Mooij,Willy M Bogers,Ronald E Bontrop,Rik A De Groen,Ernst J Verschoor,Gerrit Koopman,Andre Boonstra,Zwier M A Groothuismink,Natasja G De Groot

doi:10.1371/journal.pone.0046645

Babs E Verstrepen, Harry L A Janssen + Show 9 more

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https://doi.org/10.1371/journal.pone.0046645

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Journal: PloS one	Publication Date: Oct 30, 2012
Citations: 21	License type: CC BY 4.0

Affiliation: Biomedical Primate Research Centre, Erasmus MC

Abstract

In humans, clearance of hepatitis C virus (HCV) infection is associated with genetic variation near the IL-28B gene and the induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To study whether similar correlations exist in these animals, a direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed. All chimpanzees studied were monomorphic for the human IL-28B SNPs which are associated with spontaneous and treatment induced HCV clearance in humans. As a result, these particular SNPs cannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated with HCV-RNA load and γGT, while such correlations were not observed in humans. The correlation between IP-10, γGT and virus load in chimpanzees was not found in patients and may be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are important during HCV infection in both species. The Genbank EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B gene are HE599784 and HE599785.

Highlights

Worldwide, an estimated 170 million people are chronically infected with the hepatitis C virus (HCV) [1] and are at risk to develop liver diseases, like cirrhosis and hepatocellular carcinoma
No evidence found for the human SNPs associated with HCV clearance in chimpanzees In humans, spontaneous as well as treatment-induced clearance was found to be associated with a series of SNPs upstream of the IL-28B gene [4,5,6,8,10]
To assess whether clearance of HCV in Chimpanzees possess a unique sequence near the IL-28B gene

Summary

Introduction

An estimated 170 million people are chronically infected with the hepatitis C virus (HCV) [1] and are at risk to develop liver diseases, like cirrhosis and hepatocellular carcinoma. Genetic variation on chromosome 19, within an intergenic region upstream of the IL-28B gene, encoding for the IFN lambda 3 protein (IFNl3) correlates with both spontaneous as well as treatment-induced clearance [6,8]. Low plasma levels of interferon-gamma-inducible protein 10 (IP-10) prior to therapy predict treatment-induced clearance of HCV infection [7,11,12,13] but whether these two factors interrelate is currently under intense debate. This is highly relevant since both parameters directly interfere with antiviral IFN-pathways

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