Potential Novel N-Glycosylation Patterns Associated with the Emergence of New Genetic Variants of PRRSV-2 in the U.S.
Potential Novel N-Glycosylation Patterns Associated with the Emergence of New Genetic Variants of PRRSV-2 in the U.S.
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DOI：
10.3390/vaccines10122021
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发表时间：
2022-11-26
期刊：
影响因子：
7.8
通讯作者：
VanderWaal K
中科院分区：
文献类型：
--
作者：
Paploski IAD;Makau DN;Pamornchainavakul N;Baker JP;Schroeder D;Rovira A;VanderWaal K
蛋白质的糖基化是一个翻译后的过程，其中寡糖附着在蛋白质上，可能改变它们的折叠、表位可用性和免疫识别。在猪繁殖与呼吸综合征病毒2型（PRRSV-2）中，正选择压力作用于可能通过聚糖屏蔽与免疫逃逸相关的氨基酸位点。在这里，我们描述了潜在的n -糖基化位点随着时间的推移和在PRRSV-2的不同系统发育谱系中的模式，以更好地了解这些位点如何有助于不同谱系的共存和出现模式。我们用计算机筛选了19179个PRRSV GP5序列（2004-2021），寻找潜在的n -糖基化位点。n -糖基化位点的新组合的出现与美国过去的PRRSV流行相吻合。对于L1A谱系，残基32、33、44、51和57的糖基化首次出现在2012年，但到2015年占所有L1A序列的60%，与L1A 1-7-4菌株的出现相吻合，从2012年到2015年，L1A 1-7-4菌株的流行率从8%增加到86%。2020年出现的L1C 1-4-4菌株也具有明显的n -糖基化模式（残基32、33、44和51）。从2020年到2021年，这种模式占L1C序列的44-47%，而前几年为<5%。我们的研究结果支持了抗原进化有助于不同PRRSV菌株序列优势的假设，并且n -糖基化模式可能部分解释了菌株之间的抗原差异。需要进一步研究糖基化及其对PRRSV GP5折叠的影响，以进一步了解糖基化模式如何影响PRRSV的发生。
Glycosylation of proteins is a post-translational process where oligosaccharides are attached to proteins, potentially altering their folding, epitope availability, and immune recognition. In Porcine reproductive and respiratory syndrome virus-type 2 (PRRSV-2), positive selection pressure acts on amino acid sites potentially associated with immune escape through glycan shielding. Here, we describe the patterns of potential N-glycosylation sites over time and across different phylogenetic lineages of PRRSV-2 to better understand how these may contribute to patterns of coexistence and emergence of different lineages. We screened 19,179 PRRSV GP5 sequences (2004–2021) in silico for potential N-glycosylated sites. The emergence of novel combinations of N-glycosylated sites coincided with past PRRSV epidemics in the U.S. For lineage L1A, glycosylation at residues 32, 33, 44, 51, and 57 first appeared in 2012, but represented >62% of all L1A sequences by 2015, coinciding with the emergence of the L1A 1-7-4 strain that increased in prevalence from 8 to 86% of all L1A sequences from 2012 to 2015. The L1C 1-4-4 strain that emerged in 2020 also had a distinct N-glycosylation pattern (residues 32, 33, 44, and 51). From 2020 to 2021, this pattern was responsible for 44–47% of the L1C sequences, contrasting to <5% in years prior. Our findings support the hypothesis that antigenic evolution contributes to the sequential dominance of different PRRSV strains and that N-glycosylation patterns may partially account for antigenic differences amongst strains. Further studies on glycosylation and its effect on PRRSV GP5 folding are needed to further understand how glycosylation patterns shape PRRSV occurrence.
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