Gene expression profiling of CD4+ T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

Background: Because of the shared transmission routes, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HIV) is very common. Accumulated clinical evidence showed that one could alter the infectious course of the other virus in HIV and HCV co-infected individuals. However, little is known on the molecular basis of HIV/HCV interactions and their modulations on hosts. Methods: In this study, treatment-naive HIV, HCV mono-/co-infected individuals with CD4(+) T cell counts >300/mu l were recruited and their gene expression profiles were investigated by microarray assays. The differentially expressed genes were identified and validated by quantitative real-time PCR (qRT-PCR). To further understand the biological meanings of the gene expression profiles in these three groups, GSEA analysis (version 2.0, Broad Institute http://www.broad.mit.edu/gsea) was performed. Results: By gene set enrichment analysis, we revealed that gene sets of cell cycle progression, innate immune response and some transcription factors in CD4(+) T cells were mainly affected by HIV; while genes associated with GPCR signaling were the major targets of HCV. Metabolic pathways were modulated by both HCV and HIV viruses. Conclusions: This study for the first time offers gene profiling basis for HCV/HIV mono-/co-infections in human beings. HIV infection displayed the great impact on transcription profile of CD4(+) T cells in HIV/HCV co-infected individuals. Genes related to cell cycle arrest were significantly mediated by HIV which may lead to dysfunction of CD4(+) T cells and acceleration of HCV-related disease progression in the co-infections.