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Series GSE40711 Query DataSets for GSE40711
Status Public on Sep 30, 2012
Title Differences in cytokine production in human macrophages and in virulence in mice are attributable to the PA protein of H5N1 influenza viruses
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background. The pathogenesis of influenza A virus subtype H5N1 (hearafter, "H5N1") infection in humans is not completely understood, although hypercytokinemia is thought to play a role. We previously reported that most H5N1 viruses induce high cytokine responses in human macrophages, whereas some H5N1 viruses induce only a low level of cytokine production similar to that induced by seasonal viruses.

Methods. To identify the viral molecular determinants for cytokine induction of H5N1 viruses in human macrophages, we generated a series of reassortant viruses between the high cytokine inducer A/Vietnam/UT3028II/03 clone 2 (VN3028IIcl2) and the low inducer A/Indonesia/UT3006/05 (IDN3006), and evaluated cytokine expression in human macrophages.

Results. Viruses possessing the acidic polymerase (PA) gene of VN3028IIcl2 exhibited high levels of hypercytokinemia-related cytokine expression in human macrophages, compared with IDN3006, but showed no substantial differences in viral growth in these cells. Further, the PA gene of VN3028IIcl2 conferred enhanced virulence in mice.

Conclusions. These results demonstrate that the PA gene of VN3028IIcl2 affects cytokine production in human macrophages and virulence in mice. These findings provide new insights into the cytokine-mediated pathogenesis of H5N1 infection in humans.
Overall design Human monocyte-derived macrophages were mock-infected, or infected with IDN3006, VN3028IIcl2, or IDN3006/cl2PA at a multiplicity of infection (MOI) of 2. At 6 hours post-infection (hpi), the cells were harvested and subjected to microarray analysis (three technical replicates per each group).
Contributor(s) Takano R, Sakabe S
Citation(s) 23042757
Submission date Sep 09, 2012
Last update date Nov 27, 2018
Contact name Ryo Takano
Phone +81-155-49-5645
Organization name Obihiro University of Agriculture and Veterinary Medicine
Department National Research Center for Protozoan Diseases
Lab Research Unit for Global Infection Control
Street address Inada-cho
City Obihiro
State/province Hokkaido
ZIP/Postal code 080-8555
Country Japan
Platforms (1)
GPL13607 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
Samples (12)
GSM999592 IDN3006_6h_rep1
GSM999593 IDN3006_6h_rep2
GSM999594 IDN3006_6h_rep3
BioProject PRJNA174738

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40711_RAW.tar 42.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data provided as supplementary file

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