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The functional impairment of natural killer cells during influenza virus infection
Author(s) -
Guo Hailong,
Kumar Pawan,
Moran Thomas M,
GarciaSastre Adolfo,
Zhou Yan,
Malarkannan Subramaniam
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.60
Subject(s) - nkg2d , virus , biology , chemokine , virology , immune system , interleukin 21 , influenza a virus , nk 92 , immunology , context (archaeology) , cytotoxicity , interleukin 12 , cytokine , janus kinase 3 , cytotoxic t cell , in vitro , t cell , paleontology , biochemistry
Natural killer (NK) cells have a critical role in clearing influenza virus, which primarily infects the lung epithelial cells. However, the ability of influenza virus to infect and manipulate NK cells has not been studied. In this context, we hypothesized that influenza virus can target NK cells leading to a functional impairment in their ability to mediate cytotoxicity and cytokine/chemokine generations. Here, we show influenza virus, PR8, can enter and infect NK cells. This infection did not alter the expression levels of activating, inhibitory or developmental receptors of NK cells. However, infection of NK cells by PR8 reduced the cytotoxicity to tumor cells that represent ‘ induced‐self ’ and ‘ missing‐self ’. PR8‐infection also significantly downregulated the NCR1, NKG2D, Nkpr1c, Ly49D and CD244 receptors‐mediated generation of pro‐inflammatory cytokines and chemokines. Mutations in the non‐structural protein 1 (NS1) of influenza virus further augmented the functional impairment of NK cells. Our observations show the presence of a new, but yet to be explored, mechanism by which the influenza virus can evade immune detection.