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在体内通过非正规NF-κB信号的系统性HIV和SIV潜伏逆转

Christopher C Nixon^1,2,3, Maud Mavigner⁴, Gavin C Sampey^2,3,5,6

¹International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

|January 24, 2020

概括

用AZD5582激活NF-κB通路有效地诱导感染动物组织中的HIV和SIVRNA表达. 这种潜伏逆转策略在与清除方法相结合时有望加速艾滋病毒的根除.

科学领域:

免疫学
病毒学
药理学

背景情况:

尽管长期接受抗逆转录病毒治疗 (ART),但潜伏感染的 CD4+ T 细胞是治愈艾滋病毒的主要障碍.
目前的ART疗法需要数十年才能消除艾滋病毒的存储库,
之前试图重新激活潜伏的艾滋病毒主要集中在周围血液中,

研究的目的:

在临床前模型中研究AZD5582在潜伏HIV和SIV的活性.
评估AZD5582对血液和各种组织中的HIV/ SIVRNA表达的影响.
评估针对非正规NF- kB途径进行HIV潜伏逆转的潜力.

主要方法:

使用AZD5582治疗ART抑制的HIV和SIV rhesus的人性化小鼠.
非正规NF-κB信号通路的激活.
在血液和组织样本 (淋巴结,胸腺,骨髓,肝脏,肺部) 中分析HIV和SIVRNA表达.

主要成果:

在接受AZD5582治疗的动物血液和组织中诱导HIV和SIVRNA的表达.
在的淋巴结中观察到显著的SIVRNA表达.
在人类化小鼠的几乎所有分析组织中都发生了强烈的HIV诱导,包括淋巴结,胸腺,骨髓,肝脏和肺.

结论:

通过AZD5582激活非正规的NF-κB通路是组织中HIV/ SIV潜伏逆转的有效策略.
这种方法显著增加了病毒RNA从潜伏库中的诱导.
将延迟逆转与病毒清除工具相结合, 为加速艾滋病毒根除提供了一个有希望的途径.

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