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HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites
Virology ( IF 3.7 ) Pub Date : 2017-10-09 , DOI: 10.1016/j.virol.2017.09.026
Anjali Joshi , Emily K. Cox , Melina J. Sedano , Erin B. Punke , Raphael TC Lee , Sebastian Maurer-Stroh , Palvinder Kaur , Oon Tek Ng , Himanshu Garg

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 IC50 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.



中文翻译:

HIV-1亚型CRF01_AE和B在利用低水平的CCR5,Maraviroc敏感性和潜在的N-糖基化位点方面存在差异

HIV亚型不仅在不同的地理区域占主导地位,而且在关键的表型特征上也有所不同。为了确定信封(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,我们从新加坡的B型和AE HIV感染者中克隆了37个全长Envs。我们的数据表明,CRF01_AE Envs具有较低的潜在N糖基化位点和较高的×4发生风险。从表型上看,在表达低水平CCR5的细胞中,CRF01_AE的感染性低于B亚型Env。此外,Maraviroc IC 50对于亚型B Envs,其较高,并且与低CCR5表达细胞以及PNGS中的感染性相关。具体来说,在AE亚型和CXCR4主题病毒中,在V3环中的糖基化位点N301的出现频率较低。CRF01_AE在CCR5使用和Maraviroc易感性方面与B亚型不同,这可能对HIV发病机理和病毒进化有影响。

更新日期:2017-10-09
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