Iron inhibits replication of infectious hepatitis C virus in permissive Huh7.5.1 cells

Fillebeen, Carine; Pantopoulos, Kostas

doi:10.1016/j.jhep.2010.04.044

Cited by 64 publications

(56 citation statements)

References 42 publications

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“…1,2 In contrast, the effect of iron on HCV replication is obscure, with opposing data from in vitro studies that describe either promotion or inhibition of HCV replication in the presence of exogenous iron. [3][4][5] In clinical studies, about 30-40% of chronic HCV patients possess elevated serum iron, ferritin and transferrin saturation. 6 A correlation between increased cellular and systemic iron levels and HCV patients with poor prognosis and severe deterioration in liver metabolic processes has been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

et al. 2016

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Mechanisms that favor Hepatitis C virus (HCV) persistence over clearance are unclear, but involve defective innate immunity. Chronic infection is characterized by hepatic iron overload, hyperferraemia and hyperferittinaemia. Hepcidin modulates iron egress via ferroportin and its storage in ferritin. Chronic HCV patients have decreased hepcidin, while HCV replication is modified by HAMP silencing. We aimed to investigate interactions between HCV and hepcidin, during acute and chronic disease, and putative alterations in cellular iron homeostasis that enhance HCV propagation and promote viral persistence. Thus, we used HCV JFH-1-infected co-cultures of Huh7.5 hepatoma and THP-1 macrophage cells, HCV patients' sera and Huh7 hepcidin-expressing cells transfected with HCV replicons. Hepcidin levels were elevated in acutely infected patients, but correlated with viral load in chronic patients. HAMP expression was up-regulated early in HCV infection in vitro, with corresponding changes in ferritin and FPN. Hepcidin overexpression enhanced both viral translation and replication. In HCV-infected co-cultures, we observed increased hepcidin, reduced hepatoma ferritin and a concurrent rise in macrophaghic ferritin over time. Altered iron levels complemented amplified replication in hepatoma cells and one replication round in macrophages. Iron-loading of macrophages led to enhancement of hepatic HCV replication through reversed ferritin "flow." Viral transmissibility from infected macrophages to na€ ıve hepatoma cells was induced by iron. We propose that HCV control over iron occurs both by intracellular iron sequestration, through hepcidin, and intercellular iron mobilisation via ferritin, as means toward enhanced replication. Persistence could be achieved through HCV-induced changes in macrophagic iron that enhances viral replication in these cells.

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Section: Introductionmentioning

confidence: 99%

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

et al. 2016

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“…Enhancement of HCV translation was reported as well as promotion or inhibition of HCV replication, all of them induced by intracellular iron. 10,11 Based on experimental studies iron loading was even proposed to be a part of antiviral defense leading to limitation of HCV multiplication in chronic hepatitis C (CHC). 11 However, from the clinical point of view this argument does not find convincing evidence.…”

mentioning

confidence: 99%

“…10,11 Based on experimental studies iron loading was even proposed to be a part of antiviral defense leading to limitation of HCV multiplication in chronic hepatitis C (CHC). 11 However, from the clinical point of view this argument does not find convincing evidence. More than 40% of patients with advanced CHC present symptoms of iron overload which associate with a higher rate of liver damage, exacerbated inflammatory activity, failure of antiviral treatment with interferon, and a significant risk of hepatocarcinogenesis.…”

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confidence: 99%

The iron homeostasis network and hepatitis C virus – a new challenge in the era of directly acting antivirals

Sikorska

2016

Virulence

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“…Reduction in TfR1 accumulation and high increase in ferroportin production accompanied paradoxically by the increase both in total IRE-binding activity and IRP2 level were suggested to indicate iron deficiency in HCV replicon expressing cells. The authors hypothesized that the reduction of host intracellular iron may be a kind of virus adaptive strategy enabling its growth, especially during an early stage of infection (Fillebeen et al, 2010). Recently, Fillebeen (2010) presented an evidence for iron-induced inhibition of HCV replication in Huh7cells transfected in vitro with a consensus clone of HCV genotype 2a (JFH-1).…”

Section: Iron As a Modulator Of Hepatitis C Virus Replicationmentioning

confidence: 99%

“…The authors hypothesized that the reduction of host intracellular iron may be a kind of virus adaptive strategy enabling its growth, especially during an early stage of infection (Fillebeen et al, 2010). Recently, Fillebeen (2010) presented an evidence for iron-induced inhibition of HCV replication in Huh7cells transfected in vitro with a consensus clone of HCV genotype 2a (JFH-1). JFH-1 was derived from a Japanese patient who developed fulminant hepatitis, an extremely rare clinical presentation of HCV infection (Fillebeen et al, 2007).…”

Section: Iron As a Modulator Of Hepatitis C Virus Replicationmentioning

confidence: 99%

Pathogenesis and clinical consequences of iron overload in chronic hepatitis C -- impact of host and viral factors related to iron metabolism

Sikorska¹,

Romanowski²,

Bielawski³

2011

bta

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Chronic hepatitis C virus infection is a leading cause of progressive liver fibrosis, liver cirrhosis and hepatocellular carcinoma. Iron overload is frequently observed in cases of chronic hepatitis C and has been suggested as a negative prognostic factor for this disease. Although the mechanisms leading to iron accumulation are not fully explained yet, both host and viral factors seem to contribute towards the development of this pathology. Better understanding of the interplay between hepatitis C virus replication and expression of iron regulatory molecules may elucidate new and interesting targets for the effective treatment of chronic hepatitis C.

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Iron inhibits replication of infectious hepatitis C virus in permissive Huh7.5.1 cells

Cited by 64 publications

References 42 publications

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

The iron homeostasis network and hepatitis C virus – a new challenge in the era of directly acting antivirals

Pathogenesis and clinical consequences of iron overload in chronic hepatitis C -- impact of host and viral factors related to iron metabolism

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