HIV转录激活复制过程中差异表达LncRNA和mRNA筛选及初步分析

Screening and preliminary analysis of differentially expressed LncRNAs and mRNAs during HIV transcriptional replication

目的探讨长链非编码LncRNA和mRNA在人类免疫缺陷病毒(human immunodeficiency virus,HIV)转录激活过程中的表达情况。方法从公共数据平台Gene Expression Omnibus(GEO)下载HIV相关LncRNA+mRNA基因芯片数据集GSE74818。对其中感染时间在18h和30h的芯片探针进行重新分析,筛选出HIV从整合到基因组中到转录形成成熟病毒这一过程中差异表达的LncRNA和mRNA。采用R软件Limma包分析LncRNA和mRNA基因表达谱。结果从经过归一化、过滤和去除重复探针后筛选出1 366个差异表达基因,其中LncRNA 297个,mRNA 1 069个。LncRNA中表达上调的有188个,表达下调的有109个。mRNA表达上调的有530个,有539个表达下调。对差异表达的mRNA进行GO基因富集分析发现,在生物学过程中:主要富集在核小体、染色质组装、核小体组织、负性正性基因表达调控、表观遗传、染色质沉默等条目中;在细胞组分过程中:主要富集在核染色质、蛋白-DNA复合物、核小体、DNA包装复合物等条目中;在分子功能过程中:主要富集在蛋白异二聚体激活、核小体DNA结合条目中。KEGG pathway富集分析结果显示:差异表达的mRNA主要富集在系统性红斑狼疮、类固醇生物合成、酒精中毒、病毒致肿瘤、P53信号通路等中。结论 HIV从整合到基因组到形成成熟病毒这一过程中存在LncRNA和mRNA的差异表达,差异表达的RNA主要涉及到基因的转录调控过程和免疫通路调控过程。

Objective To study the expression of long non-coding（LncRNAs）and mRNAs during HIV transcriptional activation. Methods HIV-associated LncRNA ＋mRNA microarray data set GSE74818 was retrieved from the public data platform Gene Expression Omnibus（GEO）.Re-analysis was done for microarray data of the mock-infected cells at 18 and 30 hours after HIV infection.LncRNAs and mRNAs that were differentially expressed from HIV integrated into the host genome to the transcription of the mature virus were screened.LncRNA and mRNA expression profiles were analyzed using the Limma package software. Results A total of 1 366 differentially expressed genes were screened from normalized and duplicated probes,including297 lncRNAs and 1 069 mRNAs.Among these regulated genes,188 were up-regulated and 109 down-regulated in LncRNA while 530 up-regulated and 539 down-regulated in mRNA expression,respectively.Differentially expressed mRNAs for GO gene enrichment analysis showed nucleosome,nucleosome assembly,regulation of negative and positive gene expression,epigenetics,chromatin silencing etc.In cellular component analysis,nuclear chromatin,protein-DNA complexes,nucleosomes,DNA packaging complexes were mainly involved categories while in molecular function,protein heterodimerization activity,nucleosomal DNA binding were main groups of genes.KEGG pathway enrichment analysis found that most of the differentially expressed mRNAs enriched in pathways to systemic lupus erythematosus,steroid biosynthesis,alcoholism,viral carcinogenesis,P53-depression signaling. Conclusions There are differential expressions of LncRNA and mRNA in the process of HIV from integration into the genome to the formation of mature virus.The differentially expressed RNAs mainly involve the process of gene transcription regulation and immune pathway regulation.