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A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy

机译:经过长效抗逆转录病毒疗法治疗后成熟的巨噬细胞是人源化小鼠中主要的HIV-1细胞储库

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摘要

BackgroundDespite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc scid Il2rg tm1Wjl/SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR.
机译:背景尽管抗逆转录病毒疗法(ART)可以改善临床疗效,但静息的CD4 + T细胞仍会携带潜在的人类免疫缺陷病毒第一型(HIV-1)。但是,这类细胞不太可能是单独的病毒库,因此,确定在何处以及如何携带其他病毒对于根除措施势在必行。为此,我们使用了HIV-1ADA感染的NOD.Cg-Prkdc scid Il2rg tm1Wjl / SzJ小鼠,并用人类免疫系统对其进行了重组,以探索两种长效ART方案研究它们影响病毒细胞感染和潜伏期的能力。感染6周后,将动物分为四组。一位接受长效(LA)卡博替韦(CAB)和利比韦林(RVP)(2ART),另一位接受LA CAB,拉米夫定,阿巴卡韦和RVP(4ART),第三位未经治疗,第四位作为未感染对照。 LA ART治疗4周后,收集血液,脾脏和骨髓(BM)细胞,然后进行表型鉴定。通过液滴数字PCR分析CD4 + T细胞亚群,巨噬细胞和造血祖细胞中的HIV-1核酸。

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