Promotion of alpha/beta interferon induction during in vivo viral infection through alpha/beta interferon receptor/STAT1 system-dependent and -independent pathways

Journal of Virology
Lene MalmgaardC A Biron

Abstract

Viruses and viral components can be potent inducers of alpha/beta interferons (IFN-alpha/beta). In culture, IFN-alpha/beta prime for their own expression, in response to viruses, through interferon regulatory factor 7 (IRF-7) induction. The studies presented here evaluated the requirements for functional IFN receptors and the IFN signaling molecule STAT1 in IFN-alpha/beta induction during infections of mice with lymphocytic choriomeningitis virus (LCMV). At 24 h after infection, levels of induced IFN-alpha/beta in serum were reduced 90 to 95% in IFN-alpha/beta receptor-deficient (IFN-alpha/betaR(-/-)) and STAT1(-/-) mice compared to those in wild-type mice. However, at 48 h, these mice showed elevated expression in the serum whereas IFN-alpha/beta levels were still reduced >75% in IFN-alpha/betagammaR(-/-) mice even though the viral burden was heavy. Levels of IFN-beta, IFN-alpha4, and non-IFN-alpha4 subtype mRNA expression correlated with IFN-alpha/beta bioactivity, and all IFN-alpha/beta subtypes were coincidentally detectable. IRF-7 mRNA was induced under conditions of IFN-alpha/beta production, including late production in IFN-alpha/betaR(-/-) mice. These data demonstrate that the presence of the virus alone is not sufficie...Continue Reading

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Citations

Jan 18, 2005·Nature Medicine·Karl S LangRolf M Zinkernagel
Feb 21, 2002·The Journal of Experimental Medicine·David E Levy
Sep 12, 2007·The Journal of Experimental Medicine·Takuya MiyagiChristine A Biron
Aug 24, 2004·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Lene Malmgaard
Mar 16, 2011·Infection and Immunity·Anne-Danielle C ChesslerBarbara A Burleigh
May 17, 2011·PLoS Neglected Tropical Diseases·Allison GrosethStephan Becker
Nov 15, 2008·PLoS Pathogens·György FejerMarina A Freudenberg
Jun 29, 2007·Bioinformation·Charles D JohnsonKenneth S Ramos
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Alexander A NavariniRolf M Zinkernagel
Aug 27, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Divya MehtaSameh Basta
Oct 22, 2008·Cytokine & Growth Factor Reviews·Daniel J GoughChristopher J Clarke
Jun 21, 2007·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Alfons Billiau
Apr 2, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Lubomira LukacikovaJana Tomaskova
Feb 13, 2016·Journal of Virology·Bjoern Meyer, Hinh Ly
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Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nektarios DikopoulosJörg Reimann
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia BachUlrich Kalinke
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Nov 15, 2013·The Journal of General Virology·Amita ShortlandJonathan L Heeney

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