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HIV-1 CRF01_AE亚型和B亚型在低水平CCR5的利用、马拉维若敏感性及潜在的N-糖基化位点方面存在差异。

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites.

作者信息

Joshi Anjali, Cox Emily K, Sedano Melina J, Punke Erin B, Lee Raphael Tc, Maurer-Stroh Sebastian, Kaur Palvinder, Ng Oon Tek, Garg Himanshu

机构信息

Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA.

Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA.

出版信息

Virology. 2017 Dec;512:222-233. doi: 10.1016/j.virol.2017.09.026. Epub 2017 Oct 9.

Abstract

HIV subtypes not only predominate in different geographical regions but also differ in key phenotypic characteristics. To determine if genotypic and/or phenotypic differences in the Envelope (Env) glycoprotein can explain subtype related differences, we cloned 37 full length Envs from Subtype B and AE HIV infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs have lower Potential N Glycosylation Sites and higher risk of ×4 development. Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells expressing low levels of CCR5. Moreover, the Maraviroc IC was higher for subtype B Envs and correlated with infectivity in low CCR5 expressing cells as well as PNGS. Specifically, the glycosylation site N301 in the V3 loop was seen less frequently in AE subtype and CXCR4 topic viruses. CRF01_AE differs from B subtype in terms of CCR5 usage and Maraviroc susceptibility which may have implications for HIV pathogenesis and virus evolution.

摘要

HIV亚型不仅在不同地理区域占主导地位,而且在关键表型特征上也存在差异。为了确定包膜(Env)糖蛋白的基因型和/或表型差异是否可以解释亚型相关差异,我们从新加坡感染B亚型和AE亚型HIV的个体中克隆了37个全长Env。我们的数据表明,CRF01_AE Env具有较低的潜在N糖基化位点和较高的X4发展风险。在表型上,CRF01_AE在表达低水平CCR5的细胞中比B亚型Env的传染性更低。此外,B亚型Env的马拉维若IC更高,并且与低CCR5表达细胞中的感染性以及PNGS相关。具体而言,V3环中的糖基化位点N301在AE亚型和CXCR4嗜性病毒中出现的频率较低。CRF01_AE在CCR5使用和马拉维若敏感性方面与B亚型不同,这可能对HIV发病机制和病毒进化有影响。

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