Exon Level Transcriptomic Profiling of HIV-1-Infected CD4+ T Cells Reveals Virus-Induced Genes and Host Environment Favorable for Viral Replication

HIV-1 is extremely specialized since, even amongst CD4+ T lymphocytes (its major natural reservoir in peripheral blood), the virus productively infects only a small proportion of cells under an activated state. As the percentage of HIV-1-infected cells is very low, most studies have so far failed to capture the precise transcriptomic profile at the whole-genome scale of cells highly susceptible to virus infection. Using Affymetrix Exon array technology and a reporter virus allowing the magnetic isolation of HIV-1-infected cells, we describe the host cell factors most favorable for virus establishment and replication along with an overview of virus-induced changes in host gene expression occurring exclusively in target cells productively infected with HIV-1. We also establish that within a population of activated CD4+ T cells, HIV-1 has no detectable effect on the transcriptome of uninfected bystander cells at early time points following infection. The data gathered in this study provides unique insights into the biology of HIV-1-infected CD4+ T cells and identifies genes thought to play a determinant role in the interplay between the virus and its host. Furthermore, it provides the first catalogue of alternative splicing events found in primary human CD4+ T cells productively infected with HIV-1.HIV-1是一类高度特化的病毒：即便在CD4+ T淋巴细胞（CD4+ T lymphocytes，其在外周血中的主要天然储存库）中，该病毒也仅能在处于活化状态的极小部分细胞中实现有效感染。由于HIV-1感染细胞的比例极低，迄今为止绝大多数相关研究均未能捕获到高度易感病毒感染的细胞在全基因组尺度下的精准转录组特征。本研究采用Affymetrix外显子芯片（Affymetrix Exon array technology）技术与可实现HIV-1感染细胞磁分离的报告病毒，阐明了最有利于病毒建立感染与复制的宿主细胞因子，并全面梳理了仅在有效感染HIV-1的靶细胞中发生的、由病毒诱导的宿主基因表达变化。本研究同时证实，在活化的CD4+ T细胞群体中，感染早期阶段HIV-1对未感染旁观者细胞的转录组无任何可检测到的影响。本研究采集的数据集为HIV-1感染的CD4+ T细胞的生物学特性提供了独特的研究视角，并鉴定出在病毒与宿主的相互作用中发挥决定性作用的基因。此外，本研究还首次构建了有效感染HIV-1的原代人CD4+ T细胞中可变剪接事件的完整目录。