Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

Abstract

Purpose HIV-infected immunological non-responders (INRs) failed to achieve the normalization of CD4 + T cell counts despite their undetectable viral load. INRs have an increased risk of clinical progressions of Acquired Immunodeficiency Syndrome (AIDS) and non-AIDS events, accompanied by higher mortality rates than immunological responders (IRs). This study aimed to discover the genes, which help to distinguish INRs from IRs and explore the possible mechanism of INRs. Methods Screening DEGs between INRs and IRs using GEO microarray dataset GSE143742. DEG biological functions were investigated using GO and KEGG analysis. DEGs and WGCNA linked modules were intersected to find common genes. Key genes were identified using SVM-RFE and LASSO regression models. ROC analysis was done to evaluate key gene diagnostic effectiveness using GEO database dataset GSE106792. Cytoscape created a miRNA-mRNA-TF network for diagnostic genes. CIBERSORT and flow cytometry examined the INRs and IRs immune microenvironments. In 10 INR and 10 IR clinical samples, diagnostic gene expression was verified by RT-qPCR and Western blot. Results We obtained 190 DEGs between the INR group and IR group. Functional enrichment analysis found a significant enrichment in mitochondria and apoptosis-related pathways. CD69 and ZNF207 were identified as potential diagnostic genes. CD69 and ZNF207 shared a transcription factor, NCOR1, in the miRNA-mRNA-TF network. Immune microenvironment analysis by CIBERSORT showed that IRs had a higher level of resting memory CD4 + T cells, lower level of activated memory CD4 + T cells and resting dendritic cells than INRs, as confirmed by flow cytometry analysis. In addition, CD69 and ZNF207 were correlated with immune cells. Experiments confirmed the expression of the diagnostic genes in INRs and IRs. Conclusion CD69 and ZNF207 were identified as potential diagnostic genes to discriminate INRs from IRs. Our findings offered new clues to diagnostic and therapeutic targets for INRs.

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

“…Additionally, other bulk transcriptome investigations have identified genes related to mitochondrial and apoptotic pathways as key players in this phenomenon. [12][13][14] These findings, combined with initial evidence supporting disturbances in cytokine levels, suggest a potential mechanism underlying immunological non-responsiveness.…”

“…[6][7][8][9][10][11] Nevertheless, the mechanisms responsible for immunological non-responsiveness in a subset of HIV-infected patients remain incompletely understood, and there is still a lack of understanding regarding the status of the peripheral immune system in INRs. To address this knowledge gap, several studies have compared the transcriptomic characteristics of peripheral blood mononuclear cells (PBMCs) between IRs and INRs, [12][13][14][15] and have identified the differential expression of interferon-pathway genes, including IFI27, as likely playing a significant role in immune recovery. Nevertheless, current knowledge regarding the specific immune cell types in which these genes exhibit differential expression remains limited.…”