Pandemic H1N1 2009 Influenza A Virus Induces Weak Cytokine Responses in Human Macrophages and Dendritic Cells and Is Highly Sensitive to the Antiviral Actions of Interferons
Pandemic H1N1 2009 Influenza A Virus Induces Weak Cytokine Responses in Human Macrophages and Dendritic Cells and Is Highly Sensitive to the Antiviral Actions of Interferons
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DOI：
10.1128/jvi.01619-09
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Julkunen, Ilkka
中科院分区：
文献类型：
--
作者：
Osterlund, Pamela;Pirhonen, Jaana;Julkunen, Ilkka
在墨西哥报告首例猪源2009年甲型H1N1流感病毒感染病例后不到3个月，世卫组织宣布大流行。大流行性流感病毒在抗原性上与季节性流感病毒不同，大多数人对这种病毒缺乏免疫力。我们研究了大流行性病毒感染的人单核细胞衍生的树突状细胞（DC）和巨噬细胞中先天免疫应答的激活。大流行A/Finland/553/2009病毒代表典型的北美/欧洲谱系病毒，在这些细胞中复制得非常好。大流行性病毒以及季节性A/布里斯班/59/07（H1N1）和A/新喀里多尼亚/20/99（H1N1）病毒诱导I型（α/β干扰素[IFN-α/β]）和III型（IFN-λ 1至λ 3）IFN、CXCL 10和肿瘤坏死因子α（TNF-α）基因在DC中微弱表达。而小鼠适应的A/WSN/33（H1N1）和人类A/Udorn/72（H3 N2）病毒则有效地诱导了抗病毒和促炎基因的表达。IFN-α和IFN-β都能抑制H1N1病毒的复制。IFN-λ 3抑制病毒复制的潜力低于I型IFN。然而，大流行性病毒对抗病毒IFN-λ 3比季节性A/布里斯班/59/07（H1N1）病毒更敏感。本研究表明，新的大流行性（H1N1）甲型流感病毒可以很容易地在人的原代树突状细胞和巨噬细胞复制，并有效地避免激活先天性抗病毒反应。然而，它对IFN的抗病毒作用高度敏感，这可能为我们提供额外的手段来治疗严重的感染病例，特别是如果出现显著的耐药性。
In less than 3 months after the first cases of swine origin 2009 influenza A (H1N1) virus infections were reported from Mexico, WHO declared a pandemic. The pandemic virus is antigenically distinct from seasonal influenza viruses, and the majority of human population lacks immunity against this virus. We have studied the activation of innate immune responses in pandemic virus-infected human monocyte-derived dendritic cells (DC) and macrophages. Pandemic A/Finland/553/2009 virus, representing a typical North American/European lineage virus, replicated very well in these cells. The pandemic virus, as well as the seasonal A/Brisbane/59/07 (H1N1) and A/New Caledonia/20/99 (H1N1) viruses, induced type I (alpha/beta interferon [IFN-alpha/beta]) and type III (IFN-lambda 1 to -lambda 3) IFN, CXCL10, and tumor necrosis factor alpha (TNF-alpha) gene expression weakly in DCs. Mouse-adapted A/WSN/33 (H1N1) and human A/Udorn/72 (H3N2) viruses, instead, induced efficiently the expression of antiviral and proinflammatory genes. Both IFN-alpha and IFN-beta inhibited the replication of the pandemic (H1N1) virus. The potential of IFN-lambda 3 to inhibit viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-lambda 3 than the seasonal A/Brisbane/59/07 (H1N1) virus. The present study demonstrates that the novel pandemic (H1N1) influenza A virus can readily replicate in human primary DCs and macrophages and efficiently avoid the activation of innate antiviral responses. It is, however, highly sensitive to the antiviral actions of IFNs, which may provide us an additional means to treat severe cases of infection especially if significant drug resistance emerges.