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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.

Abstract：

: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-lambda1 to -lambda3) 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-lambda3 to inhibit viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-lambda3 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.

journal_name

J Virol

journal_title

Journal of virology

authors

Osterlund P,Pirhonen J,Ikonen N,Rönkkö E,Strengell M,Mäkelä SM,Broman M,Hamming OJ,Hartmann R,Ziegler T,Julkunen I

doi

10.1128/JVI.01619-09

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

1414-22

issue

eissn

0022-538X

issn

1098-5514

pii

JVI.01619-09

journal_volume

pub_type

杂志文章

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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.