SHIV KU-1感染恒河猴颞叶皮层中IMPDH2的表达

IMPDH2 expression in the temporal cortex in a rhesus macaque with chronic SHIV KU-1 infection

目的探讨HIV对大脑颞叶皮层神经元中次黄嘌呤核苷酸脱氢酶II(inosine monophosphate dehydrogenase 2,IMPDH2)蛋白表达的影响。方法应用MoCA分数和磁共振成像手段评估HIV感染者轻度认知障碍情况。利用中国恒河猴SHIV KU-1神经艾滋病模型,HE染色观察猴颞叶皮层细胞结构的变化;采用免疫组化方法和Western blot方法检测IMPDH2在猴颞叶皮层神经元内的表达;以及借助在线数据库预测IMPDH2相关信号通路的关键信号分子。结果HIV感染者颞叶皮质较健康对照萎缩。与健康对照相比,SHIV KU-1感染恒河猴颞叶皮层神经元中IMPDH2蛋白表达显著降低(P<0.0001)。HNRNPA1等8个基因与IMPDH2有潜在的相互作用。结论IMPDH2在HIV患者颞叶皮层神经元中的表达下调,其可能参与了HIV相关神经认知障碍发生。

Objective To investigate the effect of HIV infection on inosine-5’-monophosphate dehydrogenase 2(IMPDH2)expression in the cerebral temporal cortex.Methods Montreal Cognitive Assessment(MoCA)scores and magnetic resonance imaging were used to assess mild cognitive impairment in HIV-infected patients.In addition,the histologic structure of the temporal cortex in a rhesus macaque with chronic simian-human immunodeficiency virus(SHIV)KU-1 infection was examined using hematoxylin and eosin staining.Moreover,IMPDH2 protein expression levels in paired healthy and infected temporal cortex were examined using immunohistochemistry and Western blot.Finally,putative genes associated with IMPDH2 expression were investigated using protein-protein interaction network analysis.Results HIV-positive individuals had a thinner temporal cortex compared with healthy controls.In addition,the numbers of neurons in the temporal cortex were decreased and IMPDH2 protein levels were significantly lower in the infected monkey compared with healthy controls.Eight genes interacting with the IMPDH2 gene were identified.Conclusions Downregulation of IMPDH2 protein in the temporal cortex might be involved in the pathogenesis of HIV-related neurocognitive disease.