Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections.
1. Hyper-induction of cytokines and chemokines was found in human blood macrophages infected with the avian influenza H5N1 and H9N2/G1 viruses, as compared to those infected with human influenza H1N1 virus. 2. IRF3 played a significant role in the hyperinduction of cytokines including IFN-β, IFN-λ1,IFN-α subtypes, MCP-1, and TNF-α, and also played a part in subsequent cytokine-induced cell signalling cascades. 3. Compared with H1N1 viruses, avian influenza viruses including H5N1/97 and its precursors triggered a caspase-mediated but delayed apoptotic response in human macrophages. 4. Therapies that can minimise immunopathology-associated dysregulation of innate immunity without impairing effective host defence may be valuable adjuncts to antiviral therapy.
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
D C W
DC
Lee
A H Y
AH
Law
K
K
Hui
A H M
AH
Tam
J S M
JS
Peiris
A S Y
AS
Lau
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000095022:Interferon Lambda
D053148:Caspase 3; D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011065:Poly(ADP-ribose) Polymerases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494232:IRF3 protein, human