Jan Muzafar, Upadhyay Chitra, Hioe Catarina E
Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Research Service, James J. Peters VA Medical Center, Bronx, NY 10468, USA.
iScience. 2019 Nov 22;21:413-427. doi: 10.1016/j.isci.2019.10.030. Epub 2019 Oct 18.
The HIV-1 envelope (Env) surface is shrouded with an assortment of oligomannose-, hybrid-, and complex-type glycans that enable virus interaction with carbohydrate-recognizing lectins. This study examined the importance of glycan heterogeneity for HIV-1 transmission through the trans-infection pathway by the host mannose-binding lectin DC-SIGN. A diversity of glycan content was observed among HIV-1 strains and associated with varying degrees of trans-infection via DC-SIGN and sensitivity to trans-infection blockage by antiviral lectins. When Env glycans were modified to display only the oligomannose type, DC-SIGN-mediated virus capture was enhanced; however, virus trans-infection was diminished because of increased degradation, which was alleviated by incorporation with hybrid-type glycans. Amino acid changes in the Env signal peptide (SP) modulated the Env glycan content, leading to alterations in DC-SIGN-dependent trans-infection and virus sensitivity to antiviral lectins. Hence, SP variation and glycosylation that confer varied types of oligosaccharides to HIV-1 Env are critical determinants for virus fitness and phenotypic diversity.
HIV-1包膜（Env）表面覆盖着各种各样的低聚甘露糖型、杂合型和复合型聚糖，这些聚糖使病毒能够与碳水化合物识别凝集素相互作用。本研究通过宿主甘露糖结合凝集素DC-SIGN，探讨了聚糖异质性在HIV-1通过转染途径传播中的重要性。在HIV-1毒株中观察到多种聚糖含量，并与通过DC-SIGN进行的不同程度的转染以及对抗病毒凝集素转染阻断的敏感性相关。当Env聚糖被修饰为仅显示低聚甘露糖型时，DC-SIGN介导的病毒捕获增强；然而，由于降解增加，病毒转染减少，而与杂合型聚糖结合可缓解这种情况。Env信号肽（SP）中的氨基酸变化调节了Env聚糖含量，导致DC-SIGN依赖性转染以及病毒对抗病毒凝集素的敏感性发生改变。因此，赋予HIV-1 Env不同类型寡糖的SP变异和糖基化是病毒适应性和表型多样性的关键决定因素。
