Division of Retrovirology, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.
J Neurovirol. 2012 Apr;18(2):100-12. doi: 10.1007/s13365-012-0084-3. Epub 2012 Mar 9.
The neuropathology of simian immunodeficiency (SIV) infection in cynomolgus macaques (Macaca fascicularis) was investigated following infection with either T cell tropic SIVmacJ5, SIVmacC8 or macrophage tropic SIVmac17E-Fr. Formalin fixed, paraffin embedded brain tissue sections were analysed using a combination of in situ techniques. Macaques infected with either wild-type SIVmacJ5 or neurovirulent SIVmac17E-Fr showed evidence of neuronal dephosphorylation, loss of oligodendrocyte and CCR5 staining, lack of microglial MHC II expression, infiltration by CD4⁺ and CD8⁺ T cells and mild astrocytosis. SIVmacJ5-infected animals exhibited activation of microglia whilst those infected with SIVmac17E-Fr demonstrated a loss of microglia staining. These results are suggestive of impaired central nervous system (CNS) physiology. Furthermore, infiltration by T cells into the brain parenchyma indicated disruption of the blood brain barrier (BBB). Animals infected with the Δnef-attenuated SIVmacC8 showed microglial activation and astrogliosis indicative of an inflammatory response, lack of MHC II and CCR5 staining and infiltration by CD8⁺ T cells. These results demonstrate that the SIV infection of cynomolgus macaque can be used as a model to replicate the range of CNS pathologies observed following HIV infection of humans and to investigate the pathogenesis of HIV associated neuropathology.
对感染了嗜 T 细胞性 SIVmacJ5、SIVmacC8 或嗜巨噬细胞性 SIVmac17E-Fr 的食蟹猴（Macaca fascicularis）的猴免疫缺陷病毒（SIV）感染的神经病理学进行了研究。使用原位技术组合分析了福尔马林固定、石蜡包埋的脑组织切片。感染野生型 SIVmacJ5 或神经毒力 SIVmac17E-Fr 的猕猴表现出神经元去磷酸化、少突胶质细胞和 CCR5 染色丢失、缺乏小胶质细胞 MHC II 表达、CD4+和 CD8+T 细胞浸润和轻度星形胶质细胞增生的证据。SIVmacJ5 感染的动物表现出小胶质细胞激活，而 SIVmac17E-Fr 感染的动物则表现出小胶质细胞染色丢失。这些结果表明中枢神经系统（CNS）生理功能受损。此外，T 细胞浸润到脑实质表明血脑屏障（BBB）被破坏。感染了Δ nef 减弱的 SIVmacC8 的动物表现出小胶质细胞激活和星形胶质细胞增生，表明存在炎症反应，缺乏 MHC II 和 CCR5 染色以及 CD8+T 细胞浸润。这些结果表明，食蟹猴的 SIV 感染可用作模型来复制人类 HIV 感染后观察到的一系列 CNS 病理学，并研究 HIV 相关神经病理学的发病机制。
