中国HIV-1 B＇亚型毒株nef基因多态性及其对疾病进展影响的研究  

Study on gene polymorphism of HIV-1 B＇ nef and its influence on disease progression in northern China

作　　者：董西华[1] 韩晓旭[1] 代娣[1] 赵彬[1] 张晓丽[1] 尚红[1] 

机构地区：[1]中国医科大学附属第一医院卫生部艾滋病免疫学重点实验室,沈阳110001

出　　处：《中华微生物学和免疫学杂志》2010年第5期449-455,共7页Chinese Journal of Microbiology and Immunology

基　　金：国家科技重大专项课题资助项目（2008ZX10001-001）;国家重点基础研究发展计划（973计划）（2006CB50206）;辽宁省高等学校攀登学者（辽教发[2008]90号）

摘　　要：目的 研究我国北方地区B＇亚型HIV-1感染者病毒基因组中nef基因多态性、重要功能区的保守程度,探索其与疾病进展的关系.方法 HIV-1 B＇亚型感染长期不进展者（LTNP）30例,典型进展者（TP）42例,从全血标本中提取全前病毒DNA,经nested-PCR扩增nef基因全长,扩增产物纯化后直接测序,对测得的序列进行系统进化和氨基酸变异分析,并计算比较LTNP组与TP的HIV/AIDS组氨基酸突变位置和频率的差异.结果 nef氨基酸序列长度可变区R21K/E/H/I/Q取代,TP组突变频率（59.52%）低于LTNP组（93.33%,P〈0.005,OR=0.11）.功能区外S15R/K/N取代,TP组突变频率（64.29%）高于LTNP组（33.33%,P〈0.01,OR=3.60）;K39R/E/N取代,TP组突变频率高于LTNP组（P〈0.005）.其他功能区内有少数序列发生变异,但在两组间无差异.结论 未发现中国北方地区HIV-1 B＇亚型nef基因与疾病长期不进展相关联的明显缺失或缺陷,但nef基因序列长度可变区R21位K/E/H/I/Q取代R可能与疾病缓慢进展有关,S15R/K/N取代、K39R/E/N取代可能与疾病进展相关.nfe氨基酸序列的重要功能区较为保守.Objective To explore the polymorphism of nef gene and conservation level of functionally important domains of nef as well as their influences on HIV-1 disease progression of HIV-1 B＇infected individuals in northern China.Methods 30 long term nonprogressors（LTNPs）and 42 typical progressors （TPs）were selected.Provirus DNA was extracted from whole blood sample.The full nef gene was amplified by nested-PCR.PCR product was sequenced directly after purification.Phylogenetic analysis and amino acid sequence mutation was applied on nef sequences to explore the differences between LTNPs and TPs.Results At position 15,the S15R/K/N substitution was detected.The frequency of TPs（64.29%）wsa higher than LTNPs（33.33%,P〈0.01,0R=3.60）;R21K/E/H/I.Q,TPs and LTNPs mutation frequency was 59.52%and 93.33%（P〈0.005,OR=0.11）;At position 39,K39R/E/N was only detected in TPs（23.81%,P〈0.005）.Conclusion No significant deletion or defect associated with disease progression wsa detected in nef gene of HIV-1 B＇.But it suggested that K/E/H/I/Q mutation at 21 st amino acid of nef associated the disease nonprogression.R/K/N at 15 th amino acid of nef and R/E/N mutation at 39th amino acid of nef associated the disease progression in.HIV-1 B＇.All domaias of nef amino acids sequences were comparatively conservative.

关 键 词：人类免疫缺陷病毒1型 NEF 基因多态性 长期不进展 

分 类 号：R512.91[医药卫生—内科学]