Giuseppe
Emeritus
Inhibition of human natural killer cell activity by influenza virion and hemagglutinin. ( J Virol., abstract, edited)
6. J Virol. 2010 Feb 17. [Epub ahead of print]
Inhibition of human natural killer cell activity by influenza virion and hemagglutinin.
Mao H, Tu W, Liu Y, Qin G, Zheng J, Chan PL, Lam KT, Peiris JS, Lau YL. - Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; HKU-Pasteur Research Centre, The University of Hong Kong, Hong Kong SAR, PR China.
Natural killer (NK) cells keep viral infections under control at the early phase by directly killing infected cells. Influenza is an acute contagious respiratory viral disease transmitting from host-to-host in the first few days of infection. Evasion of host innate immune defenses including NK cells would be important for its success as a viral pathogen of humans and animals. NK cells encounter influenza virus within the micro-environment of infected cells. It is therefore important to investigate the direct effects of influenza virus on NK cell activity. Recently we demonstrated that influenza virus directly infects human NK cells and induces cell apoptosis to counter their function. Here, we further demonstrated that both the intact influenza virion and free hemagglutinin protein inhibited the cytotoxicity of fresh and IL-2-activated primary human NK cells. Hemagglutinin bound and internalized into NK cells via the sialic acids. This interaction did not decrease NKp46 expression, but caused the down-regulation of zeta chain through lysosomal pathway, which caused the decrease of NK cell cytotoxicity mediated by NKp46 and NKp30. The underlying dysregulation of signaling pathway involved zeta chain down-regulation leading to decreased Syk and ERK activation and granule exocytosis upon target cell stimulation, finally causing reduced cytotoxicity. These findings suggest that influenza virus may have developed a novel strategy to evade NK cell innate immune defense which is likely to facilitate viral transmission and may also contribute to virus pathogenesis.
PMID: 20164232 [PubMed - as supplied by publisher]
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6. J Virol. 2010 Feb 17. [Epub ahead of print]
Inhibition of human natural killer cell activity by influenza virion and hemagglutinin.
Mao H, Tu W, Liu Y, Qin G, Zheng J, Chan PL, Lam KT, Peiris JS, Lau YL. - Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; HKU-Pasteur Research Centre, The University of Hong Kong, Hong Kong SAR, PR China.
Natural killer (NK) cells keep viral infections under control at the early phase by directly killing infected cells. Influenza is an acute contagious respiratory viral disease transmitting from host-to-host in the first few days of infection. Evasion of host innate immune defenses including NK cells would be important for its success as a viral pathogen of humans and animals. NK cells encounter influenza virus within the micro-environment of infected cells. It is therefore important to investigate the direct effects of influenza virus on NK cell activity. Recently we demonstrated that influenza virus directly infects human NK cells and induces cell apoptosis to counter their function. Here, we further demonstrated that both the intact influenza virion and free hemagglutinin protein inhibited the cytotoxicity of fresh and IL-2-activated primary human NK cells. Hemagglutinin bound and internalized into NK cells via the sialic acids. This interaction did not decrease NKp46 expression, but caused the down-regulation of zeta chain through lysosomal pathway, which caused the decrease of NK cell cytotoxicity mediated by NKp46 and NKp30. The underlying dysregulation of signaling pathway involved zeta chain down-regulation leading to decreased Syk and ERK activation and granule exocytosis upon target cell stimulation, finally causing reduced cytotoxicity. These findings suggest that influenza virus may have developed a novel strategy to evade NK cell innate immune defense which is likely to facilitate viral transmission and may also contribute to virus pathogenesis.
PMID: 20164232 [PubMed - as supplied by publisher]
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