Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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1918 pandemic influenza virus and pneumococcus co-infection results in activation of coagulation and widespread pulmonary microvascular thrombosis in mice and humans

ABSTRACT: To study the effects of secondary bacterial infection during 1918 pandemic H1N1 influenza virus infection, BALB/c mice were inoculated with the fully reconstructed 1918 influenza virus followed by inoculation with pneumococcus 72h later. To study the effects of secondary bacterial infection during 1918 pandemic H1N1 influenza virus infection, BALB/c mice were inoculated with the fully reconstructed 1918 influenza virus followed by inoculation with pneumococcus 72h later.

ORGANISM(S): Mus musculus

SUBMITTER: kathie walters

PROVIDER: E-GEOD-70445 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans.

Walters Kathie-Anne KA D'Agnillo Felice F Sheng Zong-Mei ZM Kindrachuk Jason J Schwartzman Louis M LM Kuestner Rolf E RE Chertow Daniel S DS Golding Basil T BT Taubenberger Jeffery K JK Kash John C JC

The Journal of pathology 20151014 1

To study bacterial co-infection following 1918 H1N1 influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by Streptococcus pneumoniae (SP) 72 h later. Co-infected mice exhibited markedly more severe disease, shortened survival time and more severe lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co-infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed ex ...[more]

PMID: 26383585

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Project description:While pandemic 2009 H1N1 influenza A viruses were responsible for numerous severe infections in humans, these viruses do not typically cause corresponding severe disease in mammalian models. However, the generation of a virulent 2009 H1N1 virus following serial lung passage in mice has allowed for the modeling of human lung pathology in this species. Genetic determinants of mouse-adapted 2009 H1N1 viral pathogenicity have been identified, but the molecular and signaling characteristics of the host response following infection with this adapted virus have not been described. Here, we compared the gene-expression response following infection of mice with A/CA/04/2009 (CA/04) or the virulent mouse-adapted strain (MA-CA/04). Microarray analysis revealed that increased pathogenicity of MA-CA/04 was associated with: (1) early and sustained inflammatory and interferon response that could be driven in part by interferon regulatory factors (IRFs) and increased NFM-oM-^AM-+B activation, as well as inhibition of the negative regulator TRIM24, (2) early and persistent infiltration of immune cells, including inflammatory macrophages, and (3) the absence of activation of lipid metabolism later in infection, that may be mediated by nuclear receptors inhibition, including PPARG, HNF1A and 4A, with pro-inflammatory consequences. Further investigation of these signatures in the host response to other H1N1 viruses of varied pathogenicity confirmed their general relevance for virulence of influenza virus and suggested that lung response to MA-CA/04 virus was similar to that following lethal H1N1 r1918 influenza virus. This study links for the first time differential activation of IRFs, nuclear receptors, and macrophage infiltration with influenza virulence in vivo. Six-to-eight-week-old female BALB/c mice were anesthetized and inoculated with 50 M-NM-<l of phosphate-buffered saline (PBS; Mock) or with 10^6 pfu of virus in a 50 M-NM-<l volume. Nine animals per condition group were used for tarray analysis, two or three animals per time point. There were seven condition groups: A/California/04/2009, MA1-A/California/04/2009, A/Mexico/4482/09, A/Brisbane/59/07, A/New Jersey/8/76, the reconstructed 1918 virus and timeM-bM-^@M-^Smatched mocks.

Dataset Information

1918 pandemic influenza virus and pneumococcus co-infection results in activation of coagulation and widespread pulmonary microvascular thrombosis in mice and humans

Publications

1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans.

Similar Datasets

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