The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy

Bruening, Janina; Weigel, Bettina; Gerold, Gisa

doi:10.1155/2017/7232361

Cited by 32 publications

(25 citation statements)

References 138 publications

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“…Numerous reports indicated that the unfavorable IFNL3 and IFNL4 genotypes are associated with reduced response to pegIFN‐α/RBV therapy and augmented the frequency of HCV infection in PBMCs . The impact of IFNL3 rs12979860 genotypes on OCI is controversial.…”

Section: Discussionmentioning

confidence: 99%

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Ayadi

Nafari

Sakhaee

et al. 2019

Hepatology Research

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Aim The presence of occult hepatitis C virus (HCV) infection (OCI) is still controversial, however, this infection cannot be ignored. Therefore, the current study aimed at assessing the OCI frequency in patients on chronic hemodialysis (CHD) and also evaluating the association between OCI incidence with clinical parameters and interferon lambda 3/4 (IFNL3/4) gene polymorphisms. Methods A total of 515 patients on CHD and HCV negative markers were selected. Plus‐ and minus‐stranded HCV‐RNA was tested in peripheral blood mononuclear cell samples by reverse transcription–polymerase chain reaction and then genotyped using the restriction fragment length polymorphism method. Results The frequency of OCI was 11.3% in patients on CHD. Among 58 patients with OCI, 25.8%, 62.1%, and 12.1% were infected with HCV‐1a, HCV‐1b, and HCV‐3a, respectively. The mean alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were 31.9 ± 24.8, 32.3 ± 19.1, and 171.6 ± 88.9, respectively. None of the patients with OCI had a history of liver disease. Multivariate logistic regression analysis indicated that cholesterol, triglyceride, low‐density lipoprotein, 25‐hydroxyvitamin D, platelets, duration of hemodialysis, HCV subtypes, IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ΔG/ΔG genotypes were associated with OCI. Conclusion There was a moderate prevalence of OCI in Iranian patients on CHD. The current study findings indicated that this infection was associated with clinical parameters and unfavorable genotypes of IFNL3 single nucleotide polymorphisms and IFNL4 ss469415590. Further studies are required to determine the correlation between OCI incidence with clinical parameters and host genetic factors.

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Section: Discussionmentioning

confidence: 99%

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Ayadi

Nafari

Sakhaee

et al. 2019

Hepatology Research

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“…The impaired ability of neonatal pDCs to initiate an adequate antiviral immune response upon TLR‐specific activation implies clinical and immunological relevance in this infection prone population. Indeed, IL‐29 seems to be a promising candidate for the treatment of acute and chronic viral infections such as hepatitis C or E . However, based on our data, therapeutic approaches targeting IL‐29 might display reduced efficacy in neonates.…”

Section: Discussionmentioning

confidence: 94%

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Wisgrill

Wessely

Netzl

et al. 2019

Journal of Leukocyte Biology

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Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.

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“…As it comprises “cytokine‐mediated signalling pathway,” it mediates many cellular functions in HCV clearance. Interferon, lambda (IFNL) is promising cytokine‐based antiviral treatment with fewer side effect, and IFNL4 and IFNL3 polymorphisms were shown to be predictive of treatment response, further highlighting the significance of IFNL in HCV infection …”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

Sghaier

Brochot

Yacoubi-Loueslati

et al. 2019

Reviews in Medical Virology

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Summary HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.

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The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy

Cited by 32 publications

References 138 publications

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

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