Induction of innate immune responses reverses HIV cognitive disease in mice: profile by RNAseq in the brain. Induction of innate immune responses reverses HIV cognitive disease in mice: profile by RNAseq in the brain

The extent of HIV immunodeficiency and related diseases has been greatly reduced by suppressive antiretroviral therapy but roughly 50% of infected people continue to develop mild neurocognitive disorder. We established an experimental approach to investigate HIV brain disease by infection of wildtype mice with the chimeric HIV, EcoHIV. The toll-like receptor 3 ligand, polyinosinic-polycytodylic acid (poly I:C), was used to induce innate immune responses prior to or during EcoHIV infection resulting in prevention of infection or reduced virus burden and reversed behavioral disease, respectively. Here we employed RNAseq to profile brain gene expression in EcoHIV infected mice at the time of cognitive impairment and its reversal in infected, poly I:C treated mice. We confirmed RNAseq findings by QPCR of a small set of transcripts. The major pathways down-regulated by infection involved neuronal function and this dysregulation was largely reversed by poly I:C treatment. Innate immune responses were the major functional pathways induced in infected, poly I:C treated mice that were absent in infected, untreated mice. Our findings provide a framework to identify essential brain cell genes dysregulated by HIV infection and identify a complementary set of immune response genes that block infection and its associated brain disease. Overall design: To investigate the effect of Poly I:C in mice infection with the chimeric EcoHIV virus. Four groups: uninfected and infected, treated or not with Poly I:C, 3 mice each group. Brain tissue from the striatum was subjected to RNA sequencing. --------------------------- The authors have not provided information to group each sample in the respective group.

HIV免疫缺陷及相关疾病的病情严重程度已通过抑制性抗逆转录病毒疗法得到大幅缓解，但仍有约50%的感染者会进展为轻度神经认知障碍。我们建立了一种实验方法：通过用嵌合型HIV病毒EcoHIV感染野生型小鼠，以研究HIV脑部疾病。本研究使用toll样受体3（toll-like receptor 3）配体聚肌苷酸-聚胞苷酸（polyinosinic-polycytodylic acid，poly I:C），在EcoHIV感染前或感染期间诱导先天免疫应答，分别可实现感染阻断、降低病毒载量并逆转行为学疾病表型。本研究利用RNA测序（RNAseq），对出现认知障碍的EcoHIV感染小鼠，以及经poly I:C治疗后认知障碍得以逆转的感染小鼠的脑部基因表达谱进行了分析。我们通过定量PCR（QPCR）对少量转录本进行检测，验证了RNA测序的结果。感染所下调的主要通路涉及神经元功能，而该表达失调在很大程度上可被poly I:C治疗逆转。在感染且经poly I:C处理的小鼠中，先天免疫应答是主要的诱导性功能通路，而此类通路在未接受治疗的感染小鼠中并未激活。本研究结果为识别HIV感染失调的关键脑细胞基因提供了研究框架，并鉴定出一组可阻断感染及其相关脑部疾病的互补性免疫应答基因。总体实验设计：探究poly I:C对嵌合型EcoHIV病毒感染小鼠的作用。共设置4组：未感染组与感染组，各组再分为经poly I:C处理与未处理亚组，每组3只小鼠。提取纹状体脑组织进行RNA测序。--------------------------- 作者未提供各组样本的具体分组信息。