Stanley Ho Center for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
PLoS One. 2012;7(9):e45200. doi: 10.1371/journal.pone.0045200. Epub 2012 Sep 13.
Co-infection with HIV and HCV is very common. It is estimated that over 5 million people are co-infected with HIV and HCV worldwide. Accumulated evidence shows that each virus alters the course of infection of the other one. CD8+ T cells play a crucial role in the eradication of viruses and infected target cells. To the best of our knowledge, no one has investigated the gene expression profiles in HIV/HCV-co-infected individuals.
Genome-wide transcriptomes of CD8+ T cells from HIV/HCV-co-infected or mono-infected treatment-naïve individuals were analyzed by microarray assays. Pairwise comparisons were performed and differentially expressed genes were identified followed by quantitative real-time PCR (qRT-PCR) validation. Directed Acyclic Graphs (DAG) from Web-based Gene SeT AnaLysis Toolkit (WebGestalt) and DAVID bioinformatics resources 6.7 (the Database for Annotation, Visualization, and Integrated Discovery) were used to discover the Gene Ontology (GO) categories with significantly enriched gene numbers. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were also obtained by using WebGestalt software.
A total of 110, 24 and 72 transcript IDs were shown to be differentially expressed (> 2-fold and p<0.05) in comparisons between HCV- and HIV-mono-infected groups, HIV/HCV-co-infected and HIV-mono-infected groups, and HIV/HCV-co-infected and HCV-mono-infected groups, respectively. In qRT-PCR assay, most of the genes showed similar expressing profiles with the observation in microarray assays. Further analysis revealed that genes involved in cell proliferation, differentiation, transcriptional regulation and cytokine responses were significantly altered. These data offer new insights into HIV/HCV co-infections, and may help to identify new markers for the management and treatment of HIV/HCV co-infections.
HIV 和 HCV 合并感染非常常见。据估计，全世界有超过 500 万人同时感染 HIV 和 HCV。大量证据表明，每种病毒都会改变另一种病毒的感染过程。CD8+T 细胞在清除病毒和受感染的靶细胞方面发挥着至关重要的作用。据我们所知，目前还没有人研究过 HIV/HCV 合并感染个体的基因表达谱。
通过微阵列分析检测 HIV/HCV 合并感染或单感染初治个体的 CD8+T 细胞的全基因组转录组。进行了成对比较，并鉴定了差异表达基因，随后通过定量实时 PCR（qRT-PCR）进行验证。使用基于网络的基因集分析工具包（WebGestalt）和 DAVID 生物信息学资源 6.7（注释、可视化和综合发现数据库）中的有向无环图（DAG）发现基因本体论（GO）类别中具有显著富集基因数量的类别。还使用 WebGestalt 软件获得了京都基因与基因组百科全书（KEGG）途径的富集结果。
在 HCV 与 HIV 单感染组、HIV/HCV 合并感染与 HIV 单感染组、HIV/HCV 合并感染与 HCV 单感染组的比较中，分别有 110、24 和 72 个转录本 ID 被证明差异表达（>2 倍且 p<0.05）。在 qRT-PCR 检测中，大多数基因的表达谱与微阵列检测结果相似。进一步分析表明，细胞增殖、分化、转录调控和细胞因子反应相关的基因明显改变。这些数据为 HIV/HCV 合并感染提供了新的见解，并可能有助于识别 HIV/HCV 合并感染管理和治疗的新标志物。
