http://jvi.asm.org/cgi/content/abstract/JVI.01619-09v1
Pandemic H1N1 2009 Influenza A Virus Induces Weak Cytokine Response in Human Macrophages and Dendritic Cells and Is Highly Sensitive to Antiviral Actions of Interferons
Pamela ?sterlund*, Jaana Pirhonen, Niina Ikonen, Esa R?nkk?, Mari Strengell, Sanna M. M?kel?, Mia Broman, Ole J. Hamming, Rune Hartmann, Thedi Ziegler, and Ilkka Julkunen
Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland; and Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Denmark
Abstract
In less than three 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 (IFN-/) and type III (IFN-1-3) IFN, CXCL10 and TNF- 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- and IFN- inhibited the replication of the pandemic (H1N1) virus. The potential of IFN-3 to inhibit the viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-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 a significant drug resistance will emerge.
Pandemic H1N1 2009 Influenza A Virus Induces Weak Cytokine Response in Human Macrophages and Dendritic Cells and Is Highly Sensitive to Antiviral Actions of Interferons
Pamela ?sterlund*, Jaana Pirhonen, Niina Ikonen, Esa R?nkk?, Mari Strengell, Sanna M. M?kel?, Mia Broman, Ole J. Hamming, Rune Hartmann, Thedi Ziegler, and Ilkka Julkunen
Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland; and Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Denmark
Abstract
In less than three 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 (IFN-/) and type III (IFN-1-3) IFN, CXCL10 and TNF- 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- and IFN- inhibited the replication of the pandemic (H1N1) virus. The potential of IFN-3 to inhibit the viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-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 a significant drug resistance will emerge.
