Whole transcriptome analysis reveals differential gene expression profile reflecting macrophage polarization in response to influenza A H5N1 virus infection

• DOI: 10.1186/s12920-018-0335-0
• Publication Date: 2018-02-23T12:31:06Z
• Authors: Na Zhang; Yun-Juan Bao; Amy Hin-Yan Tong; Scott Zuyderduyn; Gary D. Bader; J. S. Malik Peiris; Si Lok; Suki Man-Yan Lee
• Keywords: Viral Pathogenesis; RIG-I

Avian influenza A H5N1 virus can cause lethal disease in humans. The trigger severe pneumonia and lead to acute respiratory distress syndrome. Data from clinical, vitro vivo suggest that virus-induced cytokine dysregulation could be a contributory factor the pathogenesis of human disease. However, precise mechanism infection eliciting unique host response are still not well understood. To obtain better understanding molecular events at earliest time points, we used RNA-Seq quantify compare mRNA miRNA transcriptomes induced by highly pathogenic (A/Vietnam/3212/04) or low virulent H1N1 (A/Hong Kong/54/98) viruses monocyte-derived macrophages 1-, 3-, 6-h post infection. Our data reveals two macrophage populations corresponding M1 (classically activated) M2 (alternatively subtypes respond distinctly when compared mock infection, distinction made previous microarray studies. When this confounding variable is considered our statistical model, clear set dysregulated genes pathways emerges specifically virus-infected whilst was found with Furthermore, altered expression these pathways, which have been previously implicated viral response, occurs subtype. We observe significant up-regulation RIG-I-like receptor signaling pathway. In particular, interferons, interferon-stimulated broadly affected. negative regulators interferon signaling, suppressors SOCS-1 SOCS-3, were markedly up-regulated initial round replication. Elevated levels eventual suppression cellular antiviral genes, contributing pathophysiology study provides important mechanistic insights into multi-faceted immune responses. potential candidates as therapeutic targets for treating