Ifitm3 limits the severity of acute influenza in mice.

Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited ac...

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Main Authors: Charles C Bailey, I-Chueh Huang, Christina Kam, Michael Farzan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-09-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC3435252?pdf=render
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author Charles C Bailey
I-Chueh Huang
Christina Kam
Michael Farzan
author_facet Charles C Bailey
I-Chueh Huang
Christina Kam
Michael Farzan
author_sort Charles C Bailey
collection DOAJ
description Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation.
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spelling doaj.art-cea9152cd499429cb319be41c8b827d32022-12-21T18:55:01ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-09-0189e100290910.1371/journal.ppat.1002909Ifitm3 limits the severity of acute influenza in mice.Charles C BaileyI-Chueh HuangChristina KamMichael FarzanInterferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation.http://europepmc.org/articles/PMC3435252?pdf=render
spellingShingle Charles C Bailey
I-Chueh Huang
Christina Kam
Michael Farzan
Ifitm3 limits the severity of acute influenza in mice.
PLoS Pathogens
title Ifitm3 limits the severity of acute influenza in mice.
title_full Ifitm3 limits the severity of acute influenza in mice.
title_fullStr Ifitm3 limits the severity of acute influenza in mice.
title_full_unstemmed Ifitm3 limits the severity of acute influenza in mice.
title_short Ifitm3 limits the severity of acute influenza in mice.
title_sort ifitm3 limits the severity of acute influenza in mice
url http://europepmc.org/articles/PMC3435252?pdf=render
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