Homo sapiens Transcriptome or Gene expression

Some HIV-infected individuals receiving antiretroviral therapy develop low-level viremia (LLV) which is usually defined as a plasma viral load of 50-1000 copies/ml. Peripheral blood CD4+ T cell pool is a source of LLV. However, intrinsic characteristics of CD4+ T cells in LLV patients are largely unknown. We analyzed the transcriptome profiling of peripheral blood CD4+ T cells from health controllers (HC) and HIV-infected patients receiving ART with virologic suppression (VS) or low-level viremia (LLV). To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV, KEGG pathway enrichment of differentially expressed genes (DEGs) acquired by comparing VS to HC (VS-HC) and LLV to VS (LLV-VS) were firstly analyzed and overlapped pathways between VS-HC and LLV-VS groups were obtained. DEGs in three shared pathways closely related to CD4+ T cells function, including Th1 and Th2 cell differentiation, Toll-like receptor signaling, and cytokine-cytokine receptor interaction, were further characterized. We also focused on DEGs in another two overlapped pathways, NF-kappa-B and TNF signaling pathways, both of which regulate HIV-1 infection. Finally, we evaluated the effects of 4 and 17 upregulated transcription factors in VS-HC and LLV-VS groups, respectively, on HIV-1 LTR promoter activity. Functional studies revealed that CXX5 significantly increased, while SOX5 markedly suppressed, HIV-1 transcription. Together, our results showed that CD4+ T cells in LLV patients displayed distinct mRNA profiling compared to those of VS individuals and HC, which may contribute to HIV-1 replication and reactivation of latent reservoir. Transcription factor CXXC5 and SOX5 may serve as targets for future LRAs development.