Rapid control of pandemic H1N1 influenza by targeting NKT-cells.
Rapid control of pandemic H1N1 influenza by targeting NKT-cells.
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DOI：
10.1038/srep37999
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发表时间：
2016-11-29
影响因子：
4.6
通讯作者：
Driver JP
中科院分区：
文献类型：
--
作者：
Artiaga BL;Yang G;Hutchinson TE;Loeb JC;Richt JA;Lednicky JA;Salek-Ardakani S;Driver JP
A型猪流感病毒（IAV）是猪和人类呼吸道疾病的主要原因。目前批准的抗流感疗法直接针对病毒，但这些方法正在失去效力，因为新的病毒株迅速产生耐药性。为了克服这一挑战，迫切需要更有效的抗病毒药物。在这里，我们测试了不变的自然杀伤T（NKT）细胞超级激动剂α-半乳糖神经酰胺（α-GalCer）的抗流感功效，它刺激了广泛的抗病毒免疫应答。我们发现，对感染A/加州/04/2009（CA 04）H1N1 IAV的仔猪鼻内而非全身给予α-GalCer可改善疾病症状，并使体重增加恢复至未感染猪的水平。相应地，仅在接受鼻内α-GalCer的仔猪中，上呼吸道和下呼吸道中的病毒滴度降低。最重要的是，当通过呼吸道途径靶向NKT细胞时，病毒持续存在导致的肺部炎症在很大程度上得到了预防。因此，靶向粘膜NKT细胞可能为改善感染季节性和大流行性流感病毒的猪的病程提供了一个新的有效平台，并表明这在人类中也可能是正确的，因此值得进一步研究。
Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study.
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影响因子：
4.8
作者：
Lednicky, John A.;Hamilton, Sara B.;Swayne, David E.
通讯作者：
Swayne, David E.
影响因子：
5.5
作者：
Kok, Wai Ling;Denney, Laura;Ho, Ling-Pei
通讯作者：
Ho, Ling-Pei
影响因子：
5.4
作者：
Ho, Ling-Pei;Denney, Laura;McMichael, Andrew J.
通讯作者：
McMichael, Andrew J.
DOI：
10.3390/v20801530
发表时间：
2010
期刊：
Viruses
影响因子：
--
作者：
Bouvier NM;Lowen AC
通讯作者：
Lowen AC
影响因子：
3.3
作者：
Er, C.;Skjerve, E.;Lium, B.
通讯作者：
Lium, B.