IFI27 is a potential therapeutic target for HIV infection

Abstract

Background Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health. Methods Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA. Results We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells. Conclusion The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma

“…The related pathways include the interaction between immune cells and microRNAs in the tumor microenvironment and the CCR5 pathway in macrophages [ 32 ]. GBP1 and IFI27 are also related regulatory genes involved in immunomodulation and interferon responses [ 33 , 34 ]. Among these, IFI6 and IFI44L are associated with the formation and growth of cutaneous melanoma [ 35 , 36 ].…”

Screening Biomarkers for Systemic Lupus Erythematosus Based on Machine Learning and Exploring Their Expression Correlations With the Ratios of Various Immune Cells

“…Numerous studies have demonstrated the indispensable role of IFI27 (Interferon (IFN)-a-inducible protein 27) in SLE (41)(42)(43). IFI27 is strongly correlated with the levels of T helper type 1 (Th1) cells, T helper type 2 (Th2) cells and activated dendritic cells (aDC), and the up-regulation of IFI27 is highly related to many inflammatory events induced by these immune cells (44,45). Ultimately, PLSCR1 has been found an increased expression in multiple systemic autoimmune diseases, such as primary antiphospholipid syndrome, rheumatoid arthritis, idiopathic inflammatory myopathies and SLE (46,47).…”

Identification of Key Biomarkers in Systemic Lupus Erythematosus by a Multi-Cohort Analysis

“…Moreover, IFI27, IFI44L, and ANXA3 are associated with highly expressed interferon-stimulated genes. Up-regulation of IFI27 (the interferon alpha-inducible protein27) expression may be associated with inflammatory response ( 16 ), and is involved in the progression of an HIV infection by regulating immune response ( 17 ). P-glycoprotein encoded by ABCB1 gene is an ATP-dependent drug efflux pump, which has been detected in some autoimmune disease, such as SLE ( 18 ).…”