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Journal of Virology, September 2009, p. 9215-9222, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00805-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis{triangledown}

Huawei Mao,1 Wenwei Tu,1* Gang Qin,1 Helen Ka Wai Law,1 Sin Fun Sia,1,2 Ping-Lung Chan,1 Yinping Liu,1 Kwok-Tai Lam,1 Jian Zheng,1 Malik Peiris,2,3 and Yu-Lung Lau1*

Department of Pediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, People's Republic of China,1 Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, People's Republic of China,2 HKU-Pasteur Research Centre, the University of Hong Kong, Hong Kong SAR, People's Republic of China3

Received 21 April 2009/ Accepted 30 June 2009

Influenza is an acute respiratory viral disease that is transmitted in the first few days of infection. Evasion of host innate immune defenses, including natural killer (NK) cells, is important for the virus's success as a pathogen of humans and other animals. NK cells encounter influenza viruses within the microenvironment of infected cells and are important for host innate immunity during influenza virus infection. It is therefore important to investigate the direct effects of influenza virus on NK cells. In this study, we demonstrated for the first time that influenza virus directly infects and replicates in primary human NK cells. Viral entry into NK cells was mediated by both clathrin- and caveolin-dependent endocytosis rather than through macropinocytosis and was dependent on the sialic acids on cell surfaces. In addition, influenza virus infection induced a marked apoptosis of NK cells. Our findings suggest that influenza virus can directly target and kill NK cells, a potential novel strategy of influenza virus to evade the NK cell innate immune defense that is likely to facilitate viral transmission and may also contribute to virus pathogenesis.


* Corresponding author. Mailing address for Wenwei Tu: Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Room L7-58, 7/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong SAR, People's Republic of China. Phone: (852) 2855-4205. Fax: (852) 2855-1523. E-mail: wwtu{at}hkucc.hku.hk. Mailing address for Yu-Lung Lau: Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, People's Republic of China. Phone: (852) 2819-9357. Fax: (852) 2819-8142. E-mail: lauylung{at}hkucc.hku.hk

{triangledown} Published ahead of print on 8 July 2009.


Journal of Virology, September 2009, p. 9215-9222, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00805-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.