Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy.
Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy.
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DOI：
10.1097/qad.0000000000001178
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发表时间：
2016-10-23
期刊：
影响因子：
--
通讯作者：
Almond N
中科院分区：
文献类型：
--
作者：
Ferguson D;Clarke S;Berry N;Almond N
使用猴模型，其中SIV慢性病毒载量在没有潜在神经毒性治疗的情况下自然控制，我们研究了抑制病毒血症期间发生的神经病理学事件以及这些事件何时开始。食蟹猴感染SIV毒株，自然控制到低水平的慢性病毒血症。研究1：在接种后将动物维持长达300天，并在持续抑制慢性病毒载量后分析病毒诱导的神经病理学。研究2：在SIVmacC 8感染3、10、21或125天后检查病变的开始和发展。福尔马林固定，石蜡包埋的脑切片进行分析后，免疫组化染色猴免疫缺陷病毒（SIV）（KK 41），血脑屏障渗漏，（ZO-1，纤维蛋白原），细胞凋亡（活性半胱天冬酶3）、神经炎症[GFAP、环氧合酶（考克斯）-1、考克斯-2]、小胶质细胞和巨噬细胞（Iba-1、CD 68和CD 16）、少突胶质细胞（CNPase 1）、MHC II类表达和T细胞（CD 3和CD 8）。原位杂交检测SIV的复制。研究1：尽管长期抑制病毒血症，但仍存在神经炎症。研究2：减毒SIV迅速进入脑内，引发急性期神经炎症反应。这些没有恢复到幼稚水平，并且GFAP和考克斯-2应答在病毒载量受到抑制的慢性期期间继续发展。在长时间抑制SIV病毒载量期间，以及在没有潜在神经毒性抗逆转录病毒药物的情况下，猕猴脑内存在与HIV神经认知受损患者相似的神经炎症反应。这些反应，在急性感染期间开始，不解决，尽管缺乏正在进行的外周病毒血症，潜在的重新播种的大脑。
Using simian models, where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated. Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viraemia. Study 1: animals were maintained up to 300 days after inoculation and analysed for viral-induced neuropathology following sustained suppression of chronic viral loads. Study 2: initiation and development of lesion was examined following 3, 10, 21, or 125 days SIVmacC8 infection. Formalin-fixed, paraffin-embedded brain sections were analysed following immunohistochemical staining for simian immunodeficiency virus (SIV) (KK41), blood–brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation [GFAP, cyclooxygenase (COX)-1, COX-2], microglia and macrophage (Iba-1, CD68, and CD16), oligodendrocytes (CNPase1), MHC class II expression, and T cells (CD3 and CD8). Replicating SIV was detected through in-situ hybridization. Study 1: neuroinflammation was present despite prolonged suppressed viraemia. Study 2: attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naive levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load. Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viraemia to potentially reseed the brain.
影响因子：
3.3
作者：
Li B;Berry N;Ham C;Ferguson D;Smith D;Hall J;Page M;Quartey-Papafio R;Elsley W;Robinson M;Almond N;Stebbings R
通讯作者：
Stebbings R