PDF(Pubmed)
Abstract：
The human immunodeficiency virus (HIV) envelope protein (Env) mediates viral entry into host cells and is the primary target for the humoral immune response. Env is extensively glycosylated, and these glycans shield underlying epitopes from neutralizing antibodies. The glycosylation of Env is influenced by the type of host cell in which the virus is produced. Thus, HIV is distinctly glycosylated by CD4+ T cells, the major target cells, and macrophages. However, the specific differences in glycosylation between viruses produced in these cell types have not been explored at the molecular level. Moreover, it remains unclear whether the production of HIV in CD4+ T cells or macrophages affects the efficiency of viral spread and resistance to neutralization. To address these questions, we employed the simian immunodeficiency virus (SIV) model. Glycan analysis implied higher relative levels of oligomannose-type N-glycans in SIV from CD4+ T cells (T-SIV) compared to SIV from macrophages (M-SIV), and the complex-type N-glycans profiles seem to differ between the two viruses. Notably, M-SIV demonstrated greater infectivity than T-SIV, even when accounting for Env incorporation, suggesting that host cell-dependent factors influence infectivity. Further, M-SIV was more efficiently disseminated by HIV binding cellular lectins. We also evaluated the influence of cell type-dependent differences on SIV\'s vulnerability to carbohydrate binding agents (CBAs) and neutralizing antibodies. T-SIV demonstrated greater susceptibility to mannose-specific CBAs, possibly due to its elevated expression of oligomannose-type N-glycans. In contrast, M-SIV exhibited higher susceptibility to neutralizing sera in comparison to T-SIV. These findings underscore the importance of host cell-dependent attributes of SIV, such as glycosylation, in shaping both infectivity and the potential effectiveness of intervention strategies.
摘要：
人类免疫缺陷病毒(HIV)包膜蛋白(Env)介导病毒进入宿主细胞并且是体液免疫应答的主要靶标。Env被广泛糖基化，这些聚糖保护潜在的表位免受中和抗体的影响。Env的糖基化受产生病毒的宿主细胞类型的影响。因此，HIV明显被CD4+T细胞糖基化，主要的靶细胞,和巨噬细胞。然而,在这些细胞类型中产生的病毒之间的糖基化的特定差异尚未在分子水平上进行研究。此外，目前尚不清楚CD4+T细胞或巨噬细胞中HIV的产生是否会影响病毒传播效率和抗中和性.为了解决这些问题,我们采用猿猴免疫缺陷病毒（SIV）模型。与来自巨噬细胞的SIV(M-SIV)相比,聚糖分析暗示来自CD4+T细胞(T-SIV)的SIV中的寡甘露糖型N-聚糖的相对水平更高,并且两种病毒之间的复合型N-聚糖谱似乎有所不同。值得注意的是,M-SIV表现出比T-SIV更大的传染性，即使在核算环境注册时，表明宿主细胞依赖性因素影响感染性。Further,M-SIV通过HIV结合细胞凝集素更有效地传播。我们还评估了细胞类型依赖性差异对SIV对碳水化合物结合剂（CBA）和中和抗体的脆弱性的影响。T-SIV表现出对甘露糖特异性CBAs的更大易感性，可能是由于其低聚甘露糖型N-聚糖的表达升高。相比之下,与T-SIV相比，M-SIV对中和血清表现出更高的敏感性。这些发现强调了SIV的宿主细胞依赖性属性的重要性，如糖基化，在塑造传染性和干预策略的潜在有效性方面。
