Using IPA tools to characterize molecular pathways underlying the involvement of IRF7 in antiviral response to HIV.

Objectives: Interferon Regulatory Factors (IRFs) regulate transcription of type-I interferons (IFNs) and IFN-stimulated genes. We previously reported that IFN-regulatory factor 7 (IRF7) is significantly upregulated in the brain of HIV-1 transgenic (HIV-1Tg) rats compared to F344 control rats in a region dependent manner [Li MD, Cao J, Wang S, Wang J, Sarkar S, Vigorito M, et al. Transcriptome sequencing of gene expression in the brain of the HIV-1 transgenic rat. PLoS One 2013]. The RNA deep-sequencing data were deposited in the NCBI SRA database with Gene Expression Omnibus (GEO) number GSE47474. Our current study utilized QIAGEN CLC Genomics Workbench and Ingenuity Pathway Analysis (IPA) to identify molecular pathways underlying the involvement of IRF7 in the HIV antiviral response.

Methods: The differential RNA expression data between HIV-1Tg and F344 rats as well as HAND+ and HIV+ cognitively normal patients was collected from GSE47474 and GSE152416, respectively. The "Core Expression Data Analysis" function identified the significant canonical pathways in the datasets with or without IRF7 and its 455 associated molecules.

Results: It was found that IRF7 and its 455 associated molecules altered the expression of pathways involving neurotransmission, neuronal survival, and immune function.

Conclusions: This study reveals that IRF7 is involved in the promotion of macrophage activity, neuronal differentiation, the modulation of the Th-1/Th-2 ratio, and the suppression of HIV-1 translation. Furthermore, we demonstrate that bioinformatics tools such as IPA can be employed to simulate the complete knockout of a target molecule such as IRF7 to study its involvement in biological pathways.