Ockenhouse Christian F, Bernstein Wendy B, Wang Zhining, Vahey Maryanne T
Division of Communicable Disease and Immunology, Walter Reed Army Institute of Research, Washington, DC, USA.
J Infect Dis. 2005 Jun 15;191(12):2064-74. doi: 10.1086/430321. Epub 2005 May 13.
An assessment of biomarkers from an analysis of human peripheral blood mononuclear cell gene-expression profiles was made, to acquire an understanding of transcriptional changes associated with human immunodeficiency virus type 1 (HIV-1) infection in vivo.
Supervised learning algorithms were used to create signature gene sets that could be used to distinguish seropositive from seronegative samples and delineate changes in disease status during the early stages of infection. Bioinformatic tools were used to classify persons and to functionally characterize groups of differentially expressed genes, to elucidate the impact of viral infection on host cell gene-expression patterns.
A 10-gene signature set that could be used to accurately determine the HIV-1 serostatus was identified. A 6-gene signature set was used to distinguish seropositive persons exhibiting differential changes in CD4(+) T cell counts, with 93% accuracy. Functional classification of differentially expressed genes in HIV-1 indicated a preponderance of down-regulated genes with functions related to the immune response and apoptosis. Hierarchical cluster analysis in persons whose CD4(+) T cell counts increased, compared with that in persons whose CD4(+) T cell counts decreased, was characterized by the down-regulation of genes associated with apoptosis, mitochondrial function, protein biosynthesis, and RNA binding.
Gene-expression profile analysis of a complex infectious virus, such as HIV-1, may be useful to elucidate the functional genomic relationships associated with viral infection.
通过对人类外周血单个核细胞基因表达谱进行分析来评估生物标志物，以了解与1型人类免疫缺陷病毒（HIV-1）体内感染相关的转录变化。
使用监督学习算法创建特征基因集，用于区分血清阳性和血清阴性样本，并描绘感染早期疾病状态的变化。利用生物信息学工具对人群进行分类，并对差异表达基因组进行功能表征，以阐明病毒感染对宿主细胞基因表达模式的影响。
鉴定出一个可用于准确确定HIV-1血清学状态的10基因特征集。一个6基因特征集用于区分CD4(+)T细胞计数有差异变化的血清阳性个体，准确率达93%。HIV-1中差异表达基因的功能分类表明，与免疫反应和细胞凋亡相关的功能下调基因占优势。与CD4(+)T细胞计数减少的个体相比，CD4(+)T细胞计数增加的个体的层次聚类分析特征是与细胞凋亡、线粒体功能、蛋白质生物合成和RNA结合相关的基因下调。
对诸如HIV-1这样的复杂感染病毒进行基因表达谱分析，可能有助于阐明与病毒感染相关的功能基因组关系。
