一例艾滋病痴呆综合征病人HIV-1 gp120基因多样性及生物学活性位点分析  

Analysis of Genetic Diversity and Biological Functional Site of HIV-1 gp120 from a Patient with AIDS Dementia Complex

作　　者：闫玉芬[1] 赵丽[1] 赵丽[1] 王志玉 王志玉 Michael S.McGrath[3] 侯霄煜 郑晓民 宋艳艳 姚苹 温红玲 王桂亭 许洪芝[1] 

机构地区：[1]山东大学公共卫生学院病毒学研究室,济南250012 [2]教育部实验畸形学重点实验室,济南250012 [3]Department of Laboratory Medicine,University of Californiaat San Francisco [4]济南铁路疾病预防控制所,济南250012

出　　处：《病毒学报》2009年第3期166-172,共7页Chinese Journal of Virology

基　　金：山东省科技发展项目资助(2007GG30002003)

摘　　要：为探讨人类免疫缺陷病毒1型HIV-1 gp120基因多样性和生物学活性位点与艾滋病痴呆综合征之间的关系,从一例艾滋病痴呆综合征病例尸检标本的淋巴结和中枢神经组织(大脑5个部位:颞叶灰/白质连接处、脑室周围组织、脉络丛、枕叶白质及枕叶灰/白质连接处)提取不同组织来源的基因组DNA,经PCR法扩增HIV-1 gp120基因,经克隆后挑选阳性克隆菌株,对插入片段进行测序。用生物学软件处理并绘制系统发生树,分析糖基化位点,计算ds/dn值,分析V3顶端四肽及关键位点的氨基酸。结果显示,该病人感染的病毒是HIV-1B亚型;分离自不同组织的HIV-1 gp120基因存在差异;与标准序列相比,分离自该病人的HIV-1 gp120基因的部分生物学活性位点存在改变,且源自外周淋巴组织与中枢神经组织的HIV-1 gp120基因中部分生物学活性位点也存在差异。结果表明,HIV-1 gp120基因多样性及与脑组织相关的某些生物学活性位点的改变可能与艾滋病痴呆综合征的发病机制存在一定关系。To explore the relationship between the genetic diversity and biological functional site of human immunodeficiency virus HIV-1 gp120 and the pathogenesis of AIDS dementia complex（ADC）, the full length sequences of gp120 gene was amplified with PCR from genomic DNA which was extracted from lymphoid and different brain department （periaortic lymphoid, temporal gray/white matter junction, periventricular tissue, choroids plexus, occipital white matter and occipital gray/white matter junction. ） of a patient who died of ADC. PCR products were cloned into the pGEM-T vector and positive clones were sequenced. The analysis of neighbor-joining tree, N-glycosylation sites, values of ds/dn, and loop were then all performed. The samples were all identified as HIV-1 B and genetic variation existed in HIV-1 gp120 isolated from different tissues. Compared with standard HIV-1B gp120, biological functional sites of HIV-1 gp120 isolated from the patient changed to some extent. In addition, there were differences in some biological functional sites of HIV-1 gp120 between lymphoid and brain. Therefore, genetic diversity and alterations of some biological functional sites of HIV-1 gp120 might be associated with the pathogenesis of ADC.

关 键 词：人类免疫缺陷病毒1型 HIV-1包膜糖蛋白gp120 艾滋病痴呆综合征 基因多样性 生物学活性 

分 类 号：Q987[生物学—遗传学] Q78[生物学—人类学]