Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections

• Published in: Hong Kong medical journal = Xianggang yi xue za zhi Vol. 18 Suppl 2; pp. 12 - 16
• Main Authors: Lee, D C W, Law, A H Y, Hui, K, Tam, A H M, Peiris, J S M, Lau, A S Y
• Format: Journal Article
• Language: English
• Published: China 01-02-2012
• Subjects: Apoptosis; Caspase 3 - metabolism; Cells, Cultured; Cytokines - biosynthesis; Cytokines - genetics; Gene Expression Regulation; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza, Human - metabolism; Interferon Regulatory Factor-3 - genetics; Interferon Regulatory Factor-3 - metabolism; Interferon-beta - biosynthesis; Interferon-beta - genetics; Interferons; Interleukins - biosynthesis; Interleukins - genetics; Macrophages - enzymology; Macrophages - metabolism; Macrophages - virology; Poly(ADP-ribose) Polymerases - metabolism; RNA, Messenger - metabolism; RNA, Small Interfering; Transcription Factors - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Up-Regulation - genetics
• ISSN: 1024-2708

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.