艾滋病痴呆综合征患者体内HIV-1 Nef氨基酸位点变异分析  

Analysis of amino acid sequences of HIV-1 Nef proteins from a patient with AIDS dementia complex

作　　者：贺淑婷[1] 刘建伟[1] 温红玲[1] 王志玉[1] 宋艳艳[1] 赵丽[1] 迟媛媛 蒲双双[3] 

机构地区：[1]山东大学公共卫生学院微生物检验室,济南250012 [2]青岛市妇女儿童医院检验科 [3]山东中医药大学附属医院检验科

出　　处：《中华微生物学和免疫学杂志》2014年第2期102-105,共4页Chinese Journal of Microbiology and Immunology

基　　金：山东省科技发展计划项目资助（2007GG30002003）志谢：衷心感谢美国加州大学旧金山总医院MichaelS.McGrath教授提供ADC患者尸检标本.

摘　　要：目的研究艾滋病痴呆综合征（ADC）患者体内不同部位HIV-1 nef基因变异导致氨基酸位点的改变，为研究ADC发病机制提供思路。方法克隆1例ADC病例尸检标本的外周（脾）和中枢神经系统（基底核、额叶灰质、脑膜、颞叶）共5个部位HIV-1 nef。基因并测序，利用Bioedit、MEGA4等生物学软件与HIV-1标准株HXB2Nef氨基酸序列进行比对，分析氨基酸位点变异情况。结果该ADC患者Nef蛋白某些氨基酸位点发生改变，且外周组织与中枢神经系统问及中枢神经系统不同部位问的变异情况不同，某些变异为外周和中枢所共有，某些变异仅发生在外周脾，而某些变异仅发生于中枢神经系统。这些变异可能不同程度地改变Nef蛋白某些生物学活性及功能，进而影响到HIV-1病毒的复制、感染及凋亡等。结论ADC患者体内的HIV-1 nef基因变异可导致Nef蛋白某些氨基酸位点改变，且可能对其生物学活性造成影响，这些变异是否与ADC的发病机制有关有待进-步研究。Objective：To study the mutations of HIV-1 Nef proteins at amino acid level in different sites of neural tissues derived from a patient with AIDS dementia complex （ADC） and the possible pathogenic mechanism for ADC. Methods The nef genes of HIV-1 from spleen and different brain tissues （basal ganglia, frontal gray matter, meninges and temporal lobe） of a corpse with ADC were amplified by PCR and sequenced. All sequences were analyzed by Bioedit and MEGA4 software. The mutations of HIV-1 Nef proteins at amino acid level were analyzed by comparing with the amino acid sequences of a HIV-1 standard strain HXB2. Results HIV-1 Nef proteins isolated from different tissues of the patient with ADC showed different mutations at amino acid sites. Some mutations were co-existed in tissues from spleen and brain, while others were only found in spleen or brain tissues. These mutations might affect the biological activity or function of Nef proteins at certain degree and then have an impact on the replication, infection or apoptosis of HIV-1 viruses. Conclusion The mutations of HIV-1 nef genes resulted in some amino acid changes in Nef proteins isolated from different tissues of the patient with ADC, which might affect their biological activities. However, the correlation between these mutations and the pathogenesis of ADC still needs further investigation.

关 键 词：人类免疫缺陷病毒1型 HIV-1负调控因子 艾滋病痴呆综合征 氨基酸序列 

分 类 号：R512.91[医药卫生—内科学]