An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.
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DOI:
10.1007/s13365-017-0582-4
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发表时间:
2018-04
影响因子:
3.2
通讯作者:
Mankowski JL
Mankowski JL
中科院分区:
医学4区
文献类型:
--
作者:
Beck SE;Queen SE;Metcalf Pate KA;Mangus LM;Abreu CM;Gama L;Witwer KW;Adams RJ;Zink MC;Clements JE;Mankowski JL

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猪尾猕猴的SIV感染是用于HIV神经发病机制研究的高度代表性和良好表征的动物模型,其为研究和开发HIV感染个体的HAND预后标志物提供了极好的机会。SIV研究可以在受控环境中进行,以提高重现性并提供高转化价值。与接受抗逆转录病毒治疗(ART)的HIV感染患者的观察结果相似,在接受抑制性ART治疗的SIV感染的猪尾猕猴中存在持续的神经变性和炎症。通过开发定量病毒生长测定法,测量携带有复制能力的SIV的CD 4 + T细胞和巨噬细胞,以及高度灵敏的基于小鼠的病毒生长测定法,我们已经定位了SIV/猪尾猕猴模型,以促进我们对潜伏细胞储库(包括潜在的CNS储库)的理解,从而促进HIV治愈。除了有助于我们理解HAND的发病机制外,SIV/猪尾猕猴模型还提供了一个极好的机会来测试消除大脑中潜伏的HIV储库的创新方法。
SIV infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HAND for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high translational value. Similar to observations in HIV-infected patients receiving anti-retroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.
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