Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.
Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.
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DOI：
10.1038/s41467-018-06736-7
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发表时间：
2018-10-25
影响因子：
16.6
通讯作者：
Kean LS
中科院分区：
文献类型：
--
作者：
Colonna L;Peterson CW;Schell JB;Carlson JM;Tkachev V;Brown M;Yu A;Reddy S;Obenza WM;Nelson V;Polacino PS;Mack H;Hu SL;Zeleski K;Hoffman M;Olvera J;Furlan SN;Zheng H;Taraseviciute A;Hunt DJ;Betz K;Lane JF;Vogel K;Hotchkiss CE;Moats C;Baldessari A;Murnane RD;English C;Astley CA;Wangari S;Agricola B;Ahrens J;Iwayama N;May A;Stensland L;Huang MW;Jerome KR;Kiem HP;Kean LS
同种异体移植（allo - HCT）已使一名艾滋病病毒（HIV）感染者被治愈，这引发了移植是否能根除HIV储存库的问题。为了验证这一点，我们在此展示了一个在感染猴免疫缺陷病毒（SHIV）且接受抗逆转录病毒疗法（cART）抑制的非人灵长类动物中进行同种异体移植的模型。我们用SHIV - 1157ipd3N4感染恒河猴，用cART对其进行抑制，然后在持续cART治疗期间使用主要组织相容性复合体（MHC）半相合的同种异体供体对它们进行移植。移植导致约100%的髓系供体细胞嵌合，以及高达100%的T细胞嵌合。在移植后的9到47天之间，终末分析显示，虽然移植后血液和淋巴器官中细胞相关的SHIV DNA水平降低，但SHIV储存库在包括大脑在内的多个器官中持续存在。对供体细胞和受体细胞进行分选显示，该储存库存在于受体细胞中。此外，四聚体分析表明，在持续cART治疗期间，移植后缺乏病毒特异性的供体免疫。这些结果表明，在移植后的早期，尽管存在高水平的供体细胞嵌合和移植物抗宿主病（GVHD），同种异体移植仍不足以根除受体的储存库。
同种异体造血细胞移植（allo - HCT）已使一名HIV感染者被治愈，但其潜在机制尚不清楚。在此，作者展示了一个在感染SHIV的非人灵长类动物中进行同种异体移植的模型，并表明在移植后的早期，SHIV储存库在多个组织中持续存在。
Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD. Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.
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影响因子：
16.6
作者：
Burwitz BJ;Wu HL;Abdulhaqq S;Shriver-Munsch C;Swanson T;Legasse AW;Hammond KB;Junell SL;Reed JS;Bimber BN;Greene JM;Webb GM;Northrup M;Laub W;Kievit P;MacAllister R;Axthelm MK;Ducore R;Lewis A;Colgin LMA;Hobbs T;Martin LD;Ferguson B;Thomas CR Jr;Panoskaltsis-Mortari A;Meyers G;Stanton JJ;Maziarz RT;Sacha JB
通讯作者：
Sacha JB
影响因子：
3.3
作者：
Ho O;Larsen K;Polacino P;Li Y;Anderson D;Song R;Ruprecht RM;Hu SL
通讯作者：
Hu SL
影响因子：
6.4
作者：
Henrich, Timothy J.;Hu, Zixin;Kuritzkes, Daniel R.
通讯作者：
Kuritzkes, Daniel R.
影响因子：
32.4
作者：
Calantone, Nina;Wu, Fan;Brenchley, Jason M.
通讯作者：
Brenchley, Jason M.
影响因子：
3.7
作者：
Deere, Jesse D.;Kauffman, Robert C.;North, Thomas W.
通讯作者：
North, Thomas W.