Influenza virus directly infects human natural killer cells and induces cell apoptosis.
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.
Mao
Huawei
H
Department of Paediatrics & Adolescent Medicine, the University of Hong Kong, Hong Kong SAR, People's Republic of China.
Tu
Wenwei
W
Qin
Gang
G
Law
Helen Ka Wai
HK
Sia
Sin Fun
SF
Chan
Ping-Lung
PL
Liu
Yinping
Y
Lam
Kwok-Tai
KT
Zheng
Jian
J
Peiris
Malik
M
Lau
Yu-Lung
YL
D017209:Apoptosis; D022461:Caveolins; D002966:Clathrin; D004705:Endocytosis; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000821:virology*; D009975:Orthomyxoviridae / Q000276:immunology / Q000472:pathogenicity*; D012794:Sialic Acids; D053586:Virus Internalization
D022461:Caveolins; D002966:Clathrin; D012794:Sialic Acids