tetano
Editor, Senior Moderator
April 2013, doi: 10.1128/JVI.00283-13
Visualizing the interferon-β response in mice during infection with influenza A viruses expressing or lacking nonstructural protein 1
Carsten Kallfass1,
Stefan Lienenklaus2,
Siegfried Weiss2 and
Peter Staeheli1⇑
+ Author Affiliations
1Department of Virology, University of Freiburg, 79104 Freiburg, Germany
2Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
ABSTRACT
The innate host defense against influenza virus is largely dependent on the type I interferon (IFN) system. However, surprisingly little is known about the cellular source of IFN in the infected lung. To clarify this question, we employed a reporter mouse that contains the firefly luciferase gene in place of the IFN-β coding region. IFN-β-producing cells were identified either by simultaneous immunostaining of lungs for luciferase and cellular markers or by generating conditional reporter mice that express luciferase exclusively in defined cell types. Two different strains of influenza A virus were employed that either do or do not code for nonstructural protein 1 (NS1) which strongly suppresses innate immune responses of infected cells. We found that epithelial cells and CD11c- lung macrophages that represent the prime host cells for influenza viruses showed vigorous IFN-β responses which, however, were severely reduced and delayed if the infecting virus was able to produce NS1. Interestingly, CD11c+ cell populations that were either expressing or lacking macrophage markers produced the bulk of IFN-β at 48 h post infection with wild-type influenza A virus. Our results demonstrate that the virus-encoded IFN-antagonistic factor NS1 disarms specifically epithelial cells and lung macrophages which otherwise would serve as main mediators of the early response against infection by influenza virus.
http://jvi.asm.org/content/early/2013/04/04/JVI.00283-13.abstract
Visualizing the interferon-β response in mice during infection with influenza A viruses expressing or lacking nonstructural protein 1
Carsten Kallfass1,
Stefan Lienenklaus2,
Siegfried Weiss2 and
Peter Staeheli1⇑
+ Author Affiliations
1Department of Virology, University of Freiburg, 79104 Freiburg, Germany
2Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
ABSTRACT
The innate host defense against influenza virus is largely dependent on the type I interferon (IFN) system. However, surprisingly little is known about the cellular source of IFN in the infected lung. To clarify this question, we employed a reporter mouse that contains the firefly luciferase gene in place of the IFN-β coding region. IFN-β-producing cells were identified either by simultaneous immunostaining of lungs for luciferase and cellular markers or by generating conditional reporter mice that express luciferase exclusively in defined cell types. Two different strains of influenza A virus were employed that either do or do not code for nonstructural protein 1 (NS1) which strongly suppresses innate immune responses of infected cells. We found that epithelial cells and CD11c- lung macrophages that represent the prime host cells for influenza viruses showed vigorous IFN-β responses which, however, were severely reduced and delayed if the infecting virus was able to produce NS1. Interestingly, CD11c+ cell populations that were either expressing or lacking macrophage markers produced the bulk of IFN-β at 48 h post infection with wild-type influenza A virus. Our results demonstrate that the virus-encoded IFN-antagonistic factor NS1 disarms specifically epithelial cells and lung macrophages which otherwise would serve as main mediators of the early response against infection by influenza virus.
http://jvi.asm.org/content/early/2013/04/04/JVI.00283-13.abstract