MXD1 regulates the H9N2 and H1N1 influenza A virus-induced chemokine expression and their replications in human macrophage
human infection with influenza A / Hong Kong / 156/97 (H5N1) avian influenza virus is associated with a high mortality rate of 60%. Is derived from influenza virus A / Quail / Hong Kong / G1 / 97 (H9N2 / G1) bird flu virus. Since the 1990s, four lineages of H9N2 virus has been circulating in poultry and occasionally cause infections in humans in various countries.
Due to the zoonotic potential and genetic reassortment, H9N2 / G1 and the H5N1 virus that is believed to be the candidate for the next pandemic. previous reports, including ours, show that the virulence of avian influenza virus strain correlated with their ability to express dysregulate cytokines, including TNF-α, CXCL10, and chemokines associated in cells infected with the virus.
However, the transcription factors required for cytokine dysregulation is still undefined. Given our previous report that shows the conventional role of MYC, Onco-transcription factor, to regulate the antibacterial response, we hypothesized that influenza virus induced cytokine production can be organized by members of the network MYC / MAX / MXD1. Here, we show that the influenza A / Hong Kong / 54/98 (H1N1) – or H9N2 / virus-induced G1 CXCL10 expression can be significantly attenuated by knocking out expression in macrophages MXD1 major human blood. Indeed, only the expression of MXD1 ride-regulated by both H1N1 and H9N2 / virus G1, but not MYC / MAX members / other MXD1.
The MXD1 hyperinduction CXCL10 expression and depend on MEK1 / 2 activation. By using EMSAs, we revealed that the direct MXD1 promoter derived CXCL10 binding oligonucleotide in both viral infections. Furthermore, silencing MXD1 decreased replication but not H1N1 virus H9N2. Our results provide new insights into the role MXD1 for pathogenicity avian influenza virus.
MXD1 regulates the H9N2 and H1N1 influenza A virus-induced chemokine expression and their replications in human macrophage
Off pandemic 2009 H1N1 influenza A virus vaccine has properties that are different man after homologous challenge in ferrets models
Background: The 2009 pandemic H1N1 (A (H1N1) pdm09) influenza A virus (IAV) has replaced the previous seasonal H1N1 strain in humans throughout the world and continues to circulate. Comparative performance of inactive vaccine A (H1N1) influenza pdm09 remains of considerable interest.
The purpose of this study was to evaluate the efficacy of two licensed A (H1N1) pdm09 inactivated vaccine (AS03B adjuvanted split virion Pandemrix of GlaxoSmithKline and referred to herein as (V1) and a non-adjuvanted whole virion Celvapan from Baxter and referred to herein as (V2) ) in ferrets as a pre-clinical models for human disease intervention.
Methods: Naïve ferrets were divided into two groups (V1 and V2) and immunized intramuscularly with two A / inactivated vaccine California / 07/2009 derived differently, given in a single dose V1 and V2 are given in two doses separated by 21 days. Six weeks after the first immunization, the animals vaccinated and non-vaccinated controls (NVC) group that intra-nasally challenged with 106.5 TCID50 of isolates A / England / 195/2009 A (H1N1) pdm09 with 99.1% amino acid identity to vaccine strain. clinical signs, lung histopathology, quantification of virus and antibody responses were evaluated.
Results and conclusions: The results showed important differences in the performance of both qualitative inactivated vaccine in relation to protection against challenge with the virus were comparable in naive animals (ferrets) models of human disease. V1 vaccine is limited and controlled release of the virus and reduce lower respiratory tract infection. Conversely, V2 vaccine does not control the infection and the animals showed sustained and delayed release of viral lower respiratory infection, so that lung lesions, indicating the lower efficacy of the vaccine V2.
