PDF(Pubmed)
Abstract：
BACKGROUND: Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in human immunodeficiency virus (HIV) CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation.
METHODS: Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs).
RESULTS: Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection.
CONCLUSIONS: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.
METHODS: Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs).
RESULTS: Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection.
CONCLUSIONS: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.
摘要：
背景：脑组织来源的细胞外囊泡（bdEV）在中枢神经系统（CNS）中局部起作用，并可能表明HIVCNS病理中的分子机制。使用来自猿猴免疫缺陷病毒（SIV）HIV疾病模型的脑匀浆（BH）和bdEV，我们鉴定了SIV感染和神经炎症中的RNA网络.
方法:从未感染的对照和SIV感染的受试者(有或没有CNS病理的急性和慢性期(SIV脑炎)获得死后枕骨皮质样品。根据国际共识准则对bdEV进行了分离和表征。对来自bdEV和BH的RNA进行测序和qPCR扩增以检测小RNA的水平(sRNA，包括microRNA(miRNA))和更长的RNA,包括信使RNA(mRNAs)和环状RNA(circularRNAs)。
结果：在急性和慢性感染病理组中发现BH和bdEV中异常调节的RNA，包括mRNA,miRNA,和circRNAs。bdEV中大多数失调的mRNA反映了源BH中的失调。这些mRNA不成比例地参与炎症和免疫应答。基于目标预测，来源组织中差异丰富的几种circRNAs可能是SIV感染期间bdEV中sRNA水平特异性差异的原因.
结论：bdEV和来源组织的RNA谱分析揭示了SIV感染和SIV相关CNS病理中的潜在调控网络。
方法:从未感染的对照和SIV感染的受试者(有或没有CNS病理的急性和慢性期(SIV脑炎)获得死后枕骨皮质样品。根据国际共识准则对bdEV进行了分离和表征。对来自bdEV和BH的RNA进行测序和qPCR扩增以检测小RNA的水平(sRNA，包括microRNA(miRNA))和更长的RNA,包括信使RNA(mRNAs)和环状RNA(circularRNAs)。
结果：在急性和慢性感染病理组中发现BH和bdEV中异常调节的RNA，包括mRNA,miRNA,和circRNAs。bdEV中大多数失调的mRNA反映了源BH中的失调。这些mRNA不成比例地参与炎症和免疫应答。基于目标预测，来源组织中差异丰富的几种circRNAs可能是SIV感染期间bdEV中sRNA水平特异性差异的原因.
结论：bdEV和来源组织的RNA谱分析揭示了SIV感染和SIV相关CNS病理中的潜在调控网络。
