Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA.
Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA.
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DOI：
10.1086/653213
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Clements JE
中科院分区：
文献类型：
--
作者：
Zink MC;Brice AK;Kelly KM;Queen SE;Gama L;Li M;Adams RJ;Bartizal C;Varrone J;Rabi SA;Graham DR;Tarwater PM;Mankowski JL;Clements JE
在高效抗逆转录病毒治疗（HAART）的时代，尽管血浆病毒血症得到抑制，但hiv相关中枢神经系统疾病的患病率仍在增加。使用SIV模型系统，其中所有动物在接种后3个月发生艾滋病，90%发生中枢神经系统疾病，尾尾猕猴在12天开始接受富马酸替诺福韦二氧吡酯、沙奎那韦、阿扎那韦和整合酶抑制剂治疗，并在175天开始实施安乐死。在启动HAART后，血浆和CSF病毒载量迅速下降。脑病毒RNA在尸检中检测不到，但病毒DNA水平与未治疗的siv感染猕猴没有区别。CNS炎症明显减轻，脑组织MHCⅱ类和GFAP表达降低，CSF CCL2和IL-6降低。经处理的猕猴大脑中IFNβ、I型ifn诱导基因黏液病毒（流感）抗性A （MxA）和吲哚胺2,3-双加氧酶（IDO） mRNA水平显著降低，表明免疫过度激活受到抑制，CD4+和CD8+ T细胞减少，表明外周血T细胞运输减少。脑内CD68蛋白、TNFα和IFNγ RNA水平虽然降低，但没有明显降低，表明中枢神经系统炎症持续。这些数据是在一个严格的、高病毒载量的SIV/猕猴模型中产生的，显示HAART治疗对中枢神经系统病毒复制和炎症有好处，但在一些个体中，病毒DNA水平和持续的中枢神经系统炎症没有改变。
In the era of highly active antiretroviral therapy (HAART) the prevalence of HIV-associated CNS disease has increased despite suppression of plasma viremia. Using an SIV model system where all animals develop AIDS and 90% develop CNS disease by three months postinoculation (p.i.), pigtailed macaques were treated with a regimen of tenofovir disoproxil fumarate, saquinavir, atazanavir, and an integrase inhibitor starting at 12 days and euthanized at ∼175 days p.i. Plasma and CSF viral loads declined rapidly after initiating HAART. Brain viral RNA was undetectable at necropsy but viral DNA levels were not different from untreated SIV-infected macaques. CNS inflammation was significantly reduced, with decreased brain expression of MHC Class II and GFAP and reduced CSF CCL2 and IL-6. Brain from treated macaques had significantly lower levels of IFNβ, the Type I IFN-inducible gene myxovirus (influenza) resistance A (MxA), and indolamine 2,3-dioxygenase (IDO) mRNA suggesting suppressed immune hyperactivation, and fewer CD4+ and CD8+ T cells, suggesting reduced trafficking of T cells from peripheral blood. Brain levels of CD68 protein and TNFα and IFNγ RNA, while reduced, were not significantly lower, indicating continued CNS inflammation. These data, generated in a rigorous, high viral load, SIV/macaque model showed benefits of HAART therapy on CNS virus replication and inflammation but no change in the levels of viral DNA and continued CNS inflammation in some individuals.
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影响因子：
3.2
作者：
Barber, SA;Herbst, DS;Clements, JE
通讯作者：
Clements, JE
影响因子：
64.8
作者：
Chun, TW;Carruth, L;Siliciano, RF
通讯作者：
Siliciano, RF
影响因子：
4.1
作者：
Pao, David;Pillay, Deenan;Fisher, Martin
通讯作者：
Fisher, Martin
影响因子：
--
作者：
Letendre, Scott;Marquie-Beck, Jennifer;Ellis, Ronald J.
通讯作者：
Ellis, Ronald J.
影响因子：
6.4
作者：
Barber, Sheila A.;Gama, Lucio;Clements, Janice E.
通讯作者：
Clements, Janice E.