Jacobs Lotte, Leemans Annelies, Stobbelaar Kim, Fransen Axelle, Cos Paul, Delputte Peter
Laboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, Belgium.
Pediatrics Department, Antwerp University Hospital (UZA), Wilrijkstraat 10, 2650 Edegem, Belgium.
Viruses. 2024 Nov 28;16(12):1848. doi: 10.3390/v16121848.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5-6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions. Prior research from our group showed that removing the N-glycan at position 116 (N116) in p27 led to higher neutralizing antibody responses and better protection against RSV. In this study, the effect of single, double and triple N-glycan deletion mutations in F p27 was evaluated. Surprisingly, all mutants exhibited similar expressions and functionality to the wild-type F protein. All F p27 glycomutants induced neutralizing antibodies and lowered lung viral loads after an RSV challenge in a mouse model. Although N-glycans in p27 influence immune responses, their exact role in RSV biology remains unclear. Possibly, these glycans, which are mostly conserved, play a role in other aspects of virus replication and biology.
呼吸道合胞病毒（RSV）是全球幼儿、老年人和免疫功能低下患者急性下呼吸道感染的主要原因。RSV融合（F）蛋白根据毒株不同有5至6个N糖基化位点，是疫苗开发的主要靶点。其中两到三个位点位于p27肽段，该肽段在病毒粒子中被认为不存在。我们团队之前的研究表明，去除p27中第116位（N116）的N聚糖会导致更高的中和抗体反应，并能更好地抵御RSV。在本研究中，评估了F p27中单个、双个和三个N聚糖缺失突变的效果。令人惊讶的是，所有突变体与野生型F蛋白表现出相似的表达和功能。在小鼠模型中，所有F p27糖基突变体在RSV攻击后均诱导产生中和抗体并降低了肺部病毒载量。虽然p27中的N聚糖会影响免疫反应，但其在RSV生物学中的具体作用仍不清楚。这些大多保守的聚糖可能在病毒复制和生物学的其他方面发挥作用。
