Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.

Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype alle...

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Autores principales:	Ahmad Amanzada, Waltraut Kopp, Ulrich Spengler, Giuliano Ramadori, Sabine Mihm
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/339859ca5d0748f4a076f21ffb69769c
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spelling	oai:doaj.org-article:339859ca5d0748f4a076f21ffb69769c2021-11-18T08:40:50ZInterferon-λ4 (IFNL4) transcript expression in human liver tissue samples.1932-620310.1371/journal.pone.0084026https://doaj.org/article/339859ca5d0748f4a076f21ffb69769c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376784/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, ΔG, creates a novel type III interferon (IFN) protein, IFN-λ4/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyI:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45). Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56) suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele ΔG (p<0.0001) and actual IFNL4 transcription (p = 0.0015) were found to be correlated to the activation of IFN stimulatory genes (ISGs). By contrast, IFNL4 ss469415590 genotypes were not found to be related to IFN-λ2/3/IL28 or IFN-λ1/IL29 gene expression. In conclusion, this study is the first report on intrahepatic transcript levels of the recently discovered IFNL4 gene. Data indicate that HCV infection in particular might activate IFNL4 transcription in the liver. It provides a possible explanation as to why hepatitis C patients show ISG stimulation in their livers in the apparent absence of an induction of other IFN subtypes.Ahmad AmanzadaWaltraut KoppUlrich SpenglerGiuliano RamadoriSabine MihmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84026 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahmad Amanzada Waltraut Kopp Ulrich Spengler Giuliano Ramadori Sabine Mihm Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
description	Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, ΔG, creates a novel type III interferon (IFN) protein, IFN-λ4/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyI:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45). Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56) suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele ΔG (p<0.0001) and actual IFNL4 transcription (p = 0.0015) were found to be correlated to the activation of IFN stimulatory genes (ISGs). By contrast, IFNL4 ss469415590 genotypes were not found to be related to IFN-λ2/3/IL28 or IFN-λ1/IL29 gene expression. In conclusion, this study is the first report on intrahepatic transcript levels of the recently discovered IFNL4 gene. Data indicate that HCV infection in particular might activate IFNL4 transcription in the liver. It provides a possible explanation as to why hepatitis C patients show ISG stimulation in their livers in the apparent absence of an induction of other IFN subtypes.
format	article
author	Ahmad Amanzada Waltraut Kopp Ulrich Spengler Giuliano Ramadori Sabine Mihm
author_facet	Ahmad Amanzada Waltraut Kopp Ulrich Spengler Giuliano Ramadori Sabine Mihm
author_sort	Ahmad Amanzada
title	Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
title_short	Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
title_full	Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
title_fullStr	Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
title_full_unstemmed	Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.
title_sort	interferon-λ4 (ifnl4) transcript expression in human liver tissue samples.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/339859ca5d0748f4a076f21ffb69769c
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Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples.

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