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Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China

机译：临界氨基酸残基和潜在的N-连接的糖基化位点有助于在东北部循环重组形式01_AE发病机制

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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/mul. Shorter amino acid length, fewer PNGSsandthe presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4+ cell count, and existence or coexistence ofThri 2, 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.
机译：目的：目前的研究旨在了解与东北地区循环重组形式（CRF）01_AE菌株的发病机制相关的流行病学特征和关键因素。DESIGN：CRF01_AE和非CRF01_AE样品进行了比较分析，以了解CRF01_AE的致病性特征。进行了高或低CD4 +细胞计数的CRF01_AE样品的进一步分析，具有不同的团簇用途的样品，以探讨与CRF01_AE病毒的发病机制相关的可能因素。方法：使用MEGA 6.06的系统发育分析测定新鉴定的菌株的基因型。 Geno2Pheno算法预测了团簇使用。使用在线N-Glyogical软件计算潜在的n键合糖基化位点（PNG）数。通过在线protparam工具分析氨基酸序列的性质。结果：CRF01_AE自2010年以来成为主要的HIV-1基因型。与非CRF01_AE组相比，CRF01_AE组与CD4 +电池计数小于200的较高比例的样品细胞/ MUL。较短的氨基酸长度，较少的PNGSSAND在V4中存在基本基序R / KNXT或NR / KT的存在与较低的CD4 +细胞计数相关，ARC113，VAL21和LYS33的存在或共存超过4个净电荷的存在并且缺乏V3内的PNG，对CRF01_ae病毒的X4 / R5x4团簇使用有利。结论：CRF01_AE在东北地区占HIV-1基因型。 CRF01_AE感染表现出快速疾病进展，其可以与V3和V4区的特异性氨基酸残基和PNG相关联，以及V4区的氨基酸长度。

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