IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay
The IFNL3 ( IL28B ) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the IFNL3 gene and HCV clearance. However, the mechanism underlying this association has rem...
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| Veröffentlicht in: | Nature immunology 2013-11, Vol.15 (1), p.72-79 |
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| container_title | Nature immunology |
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| creator | McFarland, Adelle P. Horner, Stacy M. Jarret, Abigail Joslyn, Rochelle C. Bindewald, Eckart Shapiro, Bruce A. Delker, Don A. Hagedorn, Curt Carrington, Mary Gale, Michael Savan, Ram |
| description | The
IFNL3
(
IL28B
) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the
IFNL3
gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the
IFNL3
mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable
IFNL3
genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment. |
| doi_str_mv | 10.1038/ni.2758 |
| format | Article |
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IFNL3
(
IL28B
) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the
IFNL3
gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the
IFNL3
mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable
IFNL3
genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.2758</identifier><identifier>PMID: 24241692</identifier><language>eng</language><ispartof>Nature immunology, 2013-11, Vol.15 (1), p.72-79</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27925,27926</link.rule.ids></links><search><creatorcontrib>McFarland, Adelle P.</creatorcontrib><creatorcontrib>Horner, Stacy M.</creatorcontrib><creatorcontrib>Jarret, Abigail</creatorcontrib><creatorcontrib>Joslyn, Rochelle C.</creatorcontrib><creatorcontrib>Bindewald, Eckart</creatorcontrib><creatorcontrib>Shapiro, Bruce A.</creatorcontrib><creatorcontrib>Delker, Don A.</creatorcontrib><creatorcontrib>Hagedorn, Curt</creatorcontrib><creatorcontrib>Carrington, Mary</creatorcontrib><creatorcontrib>Gale, Michael</creatorcontrib><creatorcontrib>Savan, Ram</creatorcontrib><title>IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay</title><title>Nature immunology</title><description>The
IFNL3
(
IL28B
) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the
IFNL3
gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the
IFNL3
mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable
IFNL3
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IFNL3
(
IL28B
) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the
IFNL3
gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the
IFNL3
mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable
IFNL3
genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment.</abstract><pmid>24241692</pmid><doi>10.1038/ni.2758</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Nature immunology, 2013-11, Vol.15 (1), p.72-79 |
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| language | eng |
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| source | Nature; Alma/SFX Local Collection |
| title | IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay |
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