Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China
Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China
复制标题
关键氨基酸残基和潜在的N联糖基化位点有助于中国东北地区循环重组01_AE发病机制
DOI：
10.1097/qad.0000000000002197
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发表时间：
2019-07-15
期刊：
影响因子：
3.8
通讯作者：
Liu, Shu-Lin
中科院分区：
文献类型：
--
作者：
Li, Qing-Hai;Shao, Bing;Liu, Shu-Lin
目的：为了解中国东北地区流行重组型（CRF）01_AE的流行病学特征及致病关键因素，设计：对CRF 01_AE与非CRF 01_AE样本进行比较分析，了解CRF 01_AE的致病性特征。进一步分析CRF01_AE高、低CD 4（+）细胞数标本之间以及不同辅助受体使用标本之间的差异，探讨与CRF01_AE病毒致病相关的可能因素。用Geno 2 Pheno算法预测辅助受体的使用。使用在线N-糖基化位点软件计算潜在N-连接糖基化位点（PNGS）数量。结果：2010年以来，CRF01_AE成为HIV-1的主要基因型。与non-CRF 01_AE组相比，CRF 01_AE组显示CD 4（+）细胞计数低于200个细胞/μ l的样本比例更高。V4的短氨基酸长度、少PNGS和R/KNXT或NR/KT基序的存在与较低的CD 4+细胞数相关，而V3中Thr 12、Arg 13、Val 21和Lys 33的存在或共存、净电荷数大于4和PNGS的缺乏有利于CRF01_AE病毒对X4/R5 X4辅助受体的利用。CRF01_AE是东北地区HIV-1基因型的优势基因型。CRF01_AE感染后病情进展较快，可能与V3、V4区的特异性氨基酸残基和PNGS以及V4区的氨基酸长度有关。版权所有（C）2019作者。由Wolters Kluwer Health，Inc.出版。
Objective: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.Design: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4(+) cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.Methods: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool.Results: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4(+) cell count less than 200 cells/mu l. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4(+) cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.Conclusion: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region. Copyright (C) 2019 The Author(s). Published by Wolters Kluwer Health, Inc.