Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

作者：Yotam Bar‐On, Ariella Glasner, Tal Meningher, Hagit Achdout, Chamutal Gur, Dikla Lankry, Alon Vitenshtein, Adrienne F. A. Meyers, Michal Mandelboim, Ofer Mandelboim · 发表于：Cell Reports · 年份：2013 · DOI：10.1016/j.celrep.2013.03.034 · 被引用次数：60 · 研究领域：Immune Cell Function and Interaction、Influenza Virus Research Studies、Respiratory viral infections research

Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide in vivo and in vitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.