title: 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.
authors: Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. pamela.osterlund@thl.fi
authors: Pamela
authors: P
authors: Osterlund
authors: Jaana
authors: J
authors: Pirhonen
authors: Niina
authors: N
authors: Ikonen
authors: Esa
authors: E
authors: Rönkkö
authors: Mari
authors: M
authors: Strengell
authors: Sanna M
authors: SM
authors: Mäkelä
authors: Mia
authors: M
authors: Broman
authors: Ole J
authors: OJ
authors: Hamming
authors: Rune
authors: R
authors: Hartmann
authors: Thedi
authors: T
authors: Ziegler
authors: Ilkka
authors: I
authors: Julkunen
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D016899:Interferon-beta; D009439:Neuraminidase