Lumngwena Evelyn Ngwa, Shuping Liliwe, Bernitz Netanya, Woodman Zenda
Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
BMC Res Notes. 2019 Jun 17;12(1):340. doi: 10.1186/s13104-019-4375-0.
As part of a larger study to understand how Envelope N-glycosylation influences HIV-1 pathogenesis, we selected a participant infected with a single Subtype C variant and determined whether deletion of specific potential N-glycan sites (PNGs) impacted Envelope function longitudinally.
We deleted five PNGs previously linked to HIV-1 transmission of two matched Envelope clones representing variants at 5 and 173 weeks post-infection. The transmitted founder (TF) had significantly better pseudovirus entry efficiency than the chronic infection (CI) variant. Deletion of all PNGs significantly reduced TF entry efficiency, binding to dendritic cell-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) receptor and trans-infection. However, mutational analysis did not affect the phenotype of the CI Envelope to the same extent. Notably, deletion of the PNGs at N241 and N448 had no effect on CI Envelope function, suggesting that some PNGs might only be important during acute infection. Therefore, vaccines that elicit antibodies against N-glycans important for TF Envelope function could drive the loss of PNGs during immune escape, abrogating viral replication. Conversely, changes in N-glycosylation might have no effect on some variants, reducing vaccine efficacy. This finding highlights the need for further investigation into the role of Envelope N-glycosylation in HIV-1 pathogenesis.
作为一项旨在了解包膜N-糖基化如何影响HIV-1发病机制的更大规模研究的一部分，我们选择了一名感染单一C亚型变体的参与者，并纵向确定特定潜在N-聚糖位点（PNG）的缺失是否会影响包膜功能。
我们删除了先前与HIV-1传播相关的五个PNG，这两个匹配的包膜克隆分别代表感染后5周和173周的变体。传播奠基者（TF）的假病毒进入效率明显高于慢性感染（CI）变体。删除所有PNG显著降低了TF的进入效率、与树突状细胞特异性细胞间粘附分子3结合非整合素（DC-SIGN）受体的能力以及转染能力。然而，突变分析对CI包膜表型的影响程度不同。值得注意的是，删除N241和N448处的PNG对CI包膜功能没有影响，这表明某些PNG可能仅在急性感染期间才重要。因此，引发针对对TF包膜功能重要的N-聚糖的抗体的疫苗可能会在免疫逃逸期间导致PNG的丢失，从而消除病毒复制。相反，N-糖基化的变化可能对某些变体没有影响，从而降低疫苗效力。这一发现凸显了进一步研究包膜N-糖基化在HIV-1发病机制中的作用的必要性。
