Figure 3.

Genes differentially expressed between low and high cytokine inducer H5N1 viruses in human macrophages. Human monocyte–derived macrophages were infected with IDN3006, VN3028IIcl2, or IDN3006/cl2PA at a multiplicity of infection of 2. At 6 hours after infection, the cells were harvested and subjected to microarray analysis. A, Gene expression levels determined by microarray are shown for the 7 cytokines tested in Figure 1. Yellow indicates P < .05, compared with the IDN3006-infected group (1-way analysis of variance [ANOVA] with the Tukey honestly significant difference (HSD) post hoc test). All values were normalized to the values of the mock group. B, A total of 129 genes were selected by 1-way ANOVA with the Tukey HSD post hoc test (P < .05) and by filtering the genes whose expression changed at least 2.0-fold relative to the level in the IDN3006-infected group. The set of genes differentially regulated in both pairs of VN3028IIcl2 and IDN3006/cl2PA as compared to IDN3006 was functionally annotated by means of Gene Ontology (GO) grouping. Statistical significance was determined by using the Fisher exact test (P < .05). C, The differentially expressed genes were connected in a de novo network based on known interactions in the Ingenuity Pathway Analysis (IPA) knowledgebase and functionally annotated by use of IPA canonical pathways. Red indicates genes whose expression showed a change of >4.0-fold for both VN3028IIcl2 and IDN3006/cl2PA, relative to IDN3006. Yellow indicates genes whose expression showed a change of >4.0-fold for IDN3006/cl2PA, relative to IDN3006. The genes enriched with the top canonical pathway of "Role of Hypercytokinemia/hyperchemokinemia in the Pathogenesis of Influenza" are boxed.