Hepatitis C Virus Infection Causes Iron Deficiency in Huh7.5.1 Cells

Matti Sällberg,Carine Fillebeen,Kostas Pantopoulos

doi:10.1371/journal.pone.0083307

Matti Sällberg, Carine Fillebeen + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0083307

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Journal: PloS one	Publication Date: Dec 13, 2013
Citations: 26	License type: CC BY 4.0

Affiliation: Jewish General Hospital, McGill University

Abstract

Patients with chronic hepatitis C virus (HCV) infection frequently develop systemic iron overload, which exacerbates morbidity. Nevertheless, iron inhibits HCV replication in cell culture models and thereby exerts antiviral activity. We hypothesized that the cellular iron status is crucial for the establishment of HCV infection. We show that HCV infection of permissive Huh7.5.1 hepatoma cells promotes an iron deficient phenotype. Thus, HCV leads to increased iron regulatory protein (IRP) activity, accumulation of IRP2 and suppression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) in the host. These data suggest that HCV regulates cellular iron levels to bypass iron-mediated inhibition in viral replication.

Highlights

hepatitis C virus (HCV) infection continues to pose a global health concern, with an estimated prevalence of 2.2–3% worldwide [1]
We address the effects of infectious HCV on iron metabolism in permissive Huh7.5.1 hepatoma cells. We demonstrate that these cells express inappropriately low hepcidin mRNA levels and develop an iron deficient phenotype in response to HCV infection
Infection of naıve Huh7.5.1 cells with HCV was accomplished by their inoculation with culture supernatant from HCV RNAtransfected Huh7.5.1 cells

Summary

Introduction

HCV infection continues to pose a global health concern, with an estimated prevalence of 2.2–3% worldwide [1]. We demonstrate that these cells express inappropriately low hepcidin mRNA levels and develop an iron deficient phenotype in response to HCV infection. This result is consistent with the reduced serum hepcidin levels in CHC patients [10], the transcriptional inactivation of hepcidin in full-length HCV Huh7.5 replicon cells [11], and the impairment of hepcidin mRNA expression in primary human hepatocytes following in vitro infection with HCV [12].

Results

Conclusion