Abstract

BackgroundBecause 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.MethodsIn this study, treatment-naive HIV, HCV mono-/co-infected individuals with CD4+ T cell counts >300/μl 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.ResultsBy 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.ConclusionsThis 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.

Highlights

  • Because of the shared transmission routes, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HIV) is very common

  • Expressed genes Microarray analysis was performed to identify the altered transcripts in 3 study groups with HIV, hepatitis C virus (HCV) monoinfection and HCV/HIV co-infections, and the raw data has been deposited in the ArrayExpress database

  • Gene set enrichment analysis To unravel the biological mechanisms differentiating between the HCV/HIV mono- and the co-infected groups, pairwise comparisons using gene set enrichment analysis (GSEA) were performed for all the three groups (HCV-mono versus HIV-mono, HCV/ HIV co-infected versus HCV-mono, HCV/HIV co-infected versus HIV-mono)

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Summary

Introduction

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. Methods: In this study, treatment-naive HIV, HCV mono-/co-infected individuals with CD4+ T cell counts >300/μl were recruited and their gene expression profiles were investigated by microarray assays. Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is very common, presumably due to their shared transmission routes (e.g., drug injection, sex behaviour) [1,2]. Accumulated evidence showed that one could alter the course of infection of the other virus in HIV and HCV co-infected individuals. The risk of hepatotoxicity from highly active antiretroviral treatment (HAART) may be increased in the co-infected patients as compared to the HIV mono-infected patients, lead to a decreased tolerability for the anti-HIV treatment [10]

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