tetano
Editor, Senior Moderator
MBio. 2014 May 20;5(3). pii: e01174-14. doi: 10.1128/mBio.01174-14.
Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses.
Menachery VD1, Eisfeld AJ2, Sch?fer A1, Josset L3, Sims AC1, Proll S3, Fan S2, Li C2, Neumann G2, Tilton SC4, Chang J3, Gralinski LE1, Long C1, Green R3, Williams CM3, Weiss J3, Matzke MM4, Webb-Robertson BJ4, Schepmoes AA4, Shukla AK4, Metz TO4, Smith RD4, Waters KM4, Katze MG, Kawaoka Y, Baric RS5.
Author information
Abstract
The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.
IMPORTANCE:
This work combines systems biology and experimental validation to identify and confirm strategies used by viruses to control the immune response. Using a novel screening approach, specific comparison between highly pathogenic influenza viruses and coronaviruses revealed similarities and differences in strategies to control the interferon and innate immune response. These findings were subsequently confirmed and explored, revealing both a common pathway of antagonism via type I interferon (IFN) delay as well as a novel avenue for control by altered histone modification. Together, the data highlight how comparative systems biology analysis can be combined with experimental validation to derive novel insights into viral pathogenesis.
Copyright ? 2014 Menachery et al.
PMID:
24846384
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24846384
Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses.
Menachery VD1, Eisfeld AJ2, Sch?fer A1, Josset L3, Sims AC1, Proll S3, Fan S2, Li C2, Neumann G2, Tilton SC4, Chang J3, Gralinski LE1, Long C1, Green R3, Williams CM3, Weiss J3, Matzke MM4, Webb-Robertson BJ4, Schepmoes AA4, Shukla AK4, Metz TO4, Smith RD4, Waters KM4, Katze MG, Kawaoka Y, Baric RS5.
Author information
Abstract
The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.
IMPORTANCE:
This work combines systems biology and experimental validation to identify and confirm strategies used by viruses to control the immune response. Using a novel screening approach, specific comparison between highly pathogenic influenza viruses and coronaviruses revealed similarities and differences in strategies to control the interferon and innate immune response. These findings were subsequently confirmed and explored, revealing both a common pathway of antagonism via type I interferon (IFN) delay as well as a novel avenue for control by altered histone modification. Together, the data highlight how comparative systems biology analysis can be combined with experimental validation to derive novel insights into viral pathogenesis.
Copyright ? 2014 Menachery et al.
PMID:
24846384
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24846384