HIV相关神经认知紊乱患者配对组织来源的HIV-1 env基因特征分析

Analysis of genetic characteristics in paired tissue-derived HIV-1 env from patients with HIV associated neurocognitive disorders

目的探讨人类免疫缺陷病毒相关神经认知紊乱(HIV associated neurocognitive disorder,HAND)患者不同组织中HIV-1 env基因的变异进化特征。方法通过国际HIV痴呆量表筛选出HAND患者,获得其血浆及脑脊液来源的HIV-1 env基因核苷酸序列,回顾性分析遗传多样性、氨基酸长度、潜在糖基化位点(PNGS)、辅助受体利用以及特征性氨基酸的特点及组织间差异。结果本研究纳入4例HAND患者共57条HIV-1 env基因V3-C4序列(血浆来源29条,脑脊液来源28条)。脑脊液中的HIV-1遗传多样性高于血浆来源毒株,差异有统计学意义(遗传多样性变异度中位数分别为0.053和0.007,P=0.043)。3例患者脑脊液与血浆来源的毒株均使用CCR5辅助受体,其中2例患者脑脊液(患者D 158 bp,患者F 158 bp)中的HIV-1 V3-C4区氨基酸长度中位数明显长于血浆来源(患者D156 bp,P=0.017;患者F 157 bp,P=0.003)。脑脊液与血浆中HIV-1 env基因序列相比共有16个氨基酸位点存在明显差异,62.5%(10/16)分布在V4区。结论 HAND患者脑脊液和血浆中的HIV-1 env基因特征存在差异,脑脊液中的HIV-1准种遗传多样性更高。

Objective To investigate the evolutionary genetic characteristics of different tissue-derived HIV-1 env from patients with HIV associated neurocognitive disorders （HAND）. Methods HIV-1 infected patients were retrospec-tively included and then identified using international HIV dementia scale score as HAND. HIV-1 env sequences that de-rived from plasma and cerebrospinal fluid （CSF） were collected to study the characteristics and differences of quasispecies diversity, amino acid length, numbers of potential N-linked glycosylation sites （PNGS） and signature pattern between the two tissues. Results Four HAND patients with 57 HIV-1 V3-C4 sequences were included in this study （plasma-de-rived：29;CSF-derived：28）. A higher diversity was noted for the variants in CSF（mean diversity：0.053） than that in plasma （mean diversity： 0.007, P= 0.043）. All viral quasispecies from three patients used CCR5 as the coreceptor in both tissues, and two patients had a longer viral amino acid length in CSF （patient D：158 bp vs. 156 bp, P= 0.017; patient F： 158 bp vs. 157 bp, P= 0.003）. Sixteen CSF-specific genetic signatures of V3-C4 region were identified in HAND patients, and most of them belonged to V4 region （10/16, 62.5%）. Conclusion Genetic characteristics are found between the two tissue-specific HIV-1 quasispecies from HAND patients, which exhibit high quasispecies diversity in CSF-derived strains.