Neuraminidase-mediated, NKp46-dependent immune-evasion mechanism of influenza viruses.

Neuraminidase-mediated, NKp46-dependent immune-evasion mechanism of influenza viruses.
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DOI:
10.1016/j.celrep.2013.03.034
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发表时间:
2013-04-25
期刊:
影响因子:
8.8
通讯作者:
Mandelboim O
Mandelboim O
中科院分区:
生物学1区
文献类型:
--
作者:
Bar-On Y;Glasner A;Meningher T;Achdout H;Gur C;Lankry D;Vitenshtein A;Meyers AFA;Mandelboim M;Mandelboim O

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自然杀伤(NK)细胞在防御流感病毒(当今已知的最致命的呼吸道病毒之一)中起着至关重要的作用。NKp46受体由NK细胞表达,对控制流感感染至关重要,因为流感病毒感染的细胞通过NKp46识别病毒血凝素(HA)蛋白而被消除。在这里,我们描述了一种由神经氨酸酶(NA)蛋白介导的流感病毒免疫逃避机制。通过使用各种NA阻滞剂,我们发现NA从NKp46中去除唾液酸残基,这导致对HA的识别降低。此外,我们提供了体内和体外证据,证明这种NA介导的、依赖NKp46的免疫逃避机制的存在,并证明NA抑制剂(通常用于治疗流感感染)不仅可以作为病毒出芽的阻滞剂,还可以作为NKp46识别的增强剂。
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.
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