Giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques.
Giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques.
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DOI：
10.1007/s13365-013-0229-z
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发表时间：
2014-02
影响因子：
3.2
通讯作者：
Westmoreland S
中科院分区：
文献类型：
--
作者：
Harbison C;Zhuang K;Gettie A;Blanchard J;Knight H;Didier P;Cheng-Mayer C;Westmoreland S
神经认知障碍，如痴呆和认知/运动障碍是与人类免疫缺陷病毒（HIV）感染相关的最重要的并发症之一，特别是在老龄化人群中，但发病机制仍然知之甚少。白质中活化的巨噬细胞和小胶质细胞以及标志性的多核巨细胞是HIV脑炎（HIVE）和几种猿免疫缺陷病毒（SIV）模型的突出特征。虽然感染的小胶质细胞已在HIVE中得到证实，但在使用SIV或嵌合猴/HIV（SHIV）毒株的恒河猴实验感染中，这种特征并不常见，限制了HIV-1发病机制和治疗研究的实用性。在这里，50只恒河猴通过三种途径之一接种了CCR 5（R5）嗜性SHIVSF 162 P3 N病毒：静脉内（n = 9）、直肠内（n = 17）或阴道内（n = 24）。43只猴出现病毒血症，26只猴出现AIDS，7只（7/26，27%）出现巨细胞SIVencephalitis（SIVE）。快速进展者表型在七只SIVE猕猴中的五只（71%）中是明显的，并且在七只猕猴中的四只（57%）中观察到利用CXCR 4辅助受体（X4辅助受体开关）的扩增。SIVE病变存在于受累动物大脑、小脑、丘脑和脑干的灰色和白色物质中。病变由病毒感染的CD 68+、CD 163+和HLA-DR+巨噬细胞组成，伴有白色物质损伤、坏死以及星形胶质细胞和小胶质细胞活化。重要的是，观察到小胶质细胞感染，这使得猕猴的R5 SHIVSF 162 P3N感染成为一种有吸引力的动物模型，不仅用于研究传播和HIVE发病机制，而且用于进行旨在从中枢神经系统（CNS）根除HIV-1的治疗干预的临床前评价。
Neurocognitive disorders such as dementia and cognitive/motor impairments are among the most significant complications associated with human immunodeficiency virus (HIV) infection, especially in aging populations, yet the pathogenesis remains poorly understood. Activated macrophages and microglia in white matter along with the hallmark multinucleated giant cells are prominent features of HIV encephalitis (HIVE) and of several simian immunodeficiency virus (SIV) models. While infected microglia have been demonstrated in HIVE, this feature is not routinely seen in experimental infections in rhesus macaques using SIV or chimeric simian/HIV (SHIV) strains, limiting utility in HIV-1 pathogenesis and treatment studies. Here, 50 rhesus macaques were inoculated with the CCR5 (R5)-tropic SHIVSF162P3N virus by one of three routes: intravenously (n=9), intrarectally (n=17), or intravaginally (n=24). Forty-three monkeys became viremic, 26 developed AIDS, and 7 (7/26, 27 %) developed giant cell SIVencephalitis (SIVE). Rapid progressor phenotype was evident in five of seven (71 %) macaques with SIVE, and expansion to utilize the CXCR4 coreceptor (X4 coreceptor switch) was observed in four out of seven (57 %). SIVE lesions were present in gray and white matter in the cerebrum, cerebellum, thalamus, and brain stem of affected animals. Lesions were composed of virally infected CD68+, CD163+, and HLA-DR+ macrophages accompanied by white matter damage, necrosis, and astroglial and microglial activation. Importantly, microglial infection was observed, which makes R5 SHIVSF162P3N infection of macaques an attractive animal model not only to study transmission and HIVE pathogenesis but also to conduct preclinical evaluation of therapeutic interventions aimed at eradicating HIV-1 from the central nervous system (CNS).
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影响因子：
6.7
作者：
Schnell G;Joseph S;Spudich S;Price RW;Swanstrom R
通讯作者：
Swanstrom R
影响因子：
11.2
作者：
Churchill, Melissa J.;Wesselingh, Steven L.;Gorry, Paul R.
通讯作者：
Gorry, Paul R.
影响因子：
5.4
作者：
Shakirzyanova, Madina;Tsai, Lily;Cheng-Mayer, Cecilia
通讯作者：
Cheng-Mayer, Cecilia
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.
影响因子：
6.4
作者：
Günthard, HF;Havlir, DV;Wong, JK
通讯作者：
Wong, JK