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'Rinse and Replace': Boosting T Cell Turnover To Reduce HIV-1 Reservoirs.
Trends in Immunology ( IF 13.1 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.it.2020.04.003
Zvi Grossman 1 , Nevil J Singh 2 , Francesco R Simonetti 3 , Michael M Lederman 4 , Daniel C Douek 5 , Steven G Deeks 6 ,
Affiliation  

Latent HIV-1 persists indefinitely during antiretroviral therapy (ART) as an integrated silent genome in long-lived memory CD4+ T cells. In untreated infections, immune activation increases the turnover of intrinsically long-lived provirus-containing CD4+ T cells. Those are 'washed out' as a result of their activation, which when coupled to viral protein expression can facilitate local inflammation and recruitment of uninfected cells to activation sites, causing latently infected cells to compete for survival. De novo infection can counter this washout. During ART, inflammation and CD4+ T cell activation wane, resulting in reduced cell turnover and a persistent reservoir. We propose accelerating reservoir washout during ART by triggering sequential waves of polyclonal CD4+ T cell activation while simultaneously enhancing virus protein expression. Reservoir reduction as an adjunct to other therapies might achieve lifelong viral control.

中文翻译:

“冲洗和更换”:促进 T 细胞周转以减少 HIV-1 病毒库。

潜伏的 HIV-1 在抗逆转录病毒治疗 (ART) 期间无限期地持续存在,作为长寿命记忆 CD4+ T 细胞中的整合沉默基因组。在未经治疗的感染中,免疫激活会增加本质上长寿的原病毒 CD4+ T 细胞的周转率。这些病毒由于激活而被“洗掉”,当与病毒蛋白表达结合时,可以促进局部炎症并将未感染的细胞招募到激活位点,从而导致潜伏感染的细胞竞争生存。从头感染可以对抗这种冲刷。在 ART 期间,炎症和 CD4+ T 细胞活化减弱,导致细胞更新减少和持久储存。我们建议通过触发多克隆 CD4+ T 细胞的连续激活波同时增强病毒蛋白表达来加速 ART 期间的储库清除。减少病毒库作为其他疗法的辅助手段可能会实现终生病毒控制。
更新日期:2020-05-12
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