Differential Impact of Spike Protein Mutations on SARS-CoV-2 Infectivity and Immune Evasion: Insights from Delta and Kappa Variants.

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Journal of microbiology and biotechnology Pub Date : 2024-12-28 Epub Date: 2024-12-02 DOI:10.4014/jmb.2411.11001
Tae-Hun Kim, Sojung Bae, Jinjong Myoung
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引用次数: 0

Abstract

SARS-CoV-2 continues to pose a global health challenge due to its high transmissibility and mutability, with new variants emerging that potentially undermine vaccination and therapeutic efforts. Mutations in the spike protein, particularly in the receptor-binding domain (RBD), significantly influence viral transmissibility and immune escape. However, the complex interplay of these mutations and their combined effects on viral fitness remain to be analyzed. In this study, we investigated the functional impact of key mutations found in the Delta and Kappa variants of SARS-CoV-2. Using pseudovirus assays, we demonstrated that the T478K and L452R mutations characteristic of the Delta variant primarily enhance viral infectivity, with minimal effect on antibody-mediated neutralization. Conversely, the E484Q mutation of the Kappa variant, alone or in combination with L452R, significantly improved evasion of antibody-mediated neutralization but appeared to compromise viral fitness and infectivity. Notably, contrary to previous reports, we found that the P681R mutation contributed neither to increased infectivity nor immune evasion at least in the assay system employed in this study. Our findings suggest that the Delta variant's global dominance over the Kappa variant may be attributed to its superior infectivity and transmissibility rather than enhanced immune evasion capabilities. These results provide valuable insights into the functional consequences of spike protein mutations and may aid in predicting the emergence and spread of future SARS-CoV-2 variants. Such understanding is crucial for enhancing public health preparedness and informing the development of next-generation vaccines and therapeutics.

刺突蛋白突变对SARS-CoV-2传染性和免疫逃避的差异影响:来自Delta和Kappa变异的见解
由于SARS-CoV-2的高传播性和易变性,它继续构成全球卫生挑战,新变种的出现可能会破坏疫苗接种和治疗工作。刺突蛋白的突变,特别是受体结合域(RBD)的突变,显著影响病毒的传播性和免疫逃逸。然而,这些突变的复杂相互作用及其对病毒适应性的综合影响仍有待分析。在这项研究中,我们研究了SARS CoV-2的Delta和Kappa变体中发现的关键突变对功能的影响。通过假病毒实验,我们证明了Delta变异的T478K和L452R突变特征主要增强了病毒的传染性,对抗体介导的中和作用影响很小。相反,Kappa变异的E484Q突变,单独或与L452R联合,显著改善了抗体介导的中和逃避,但似乎损害了病毒的适应性和传染性。值得注意的是,与之前的报道相反,我们发现P681R突变既不会增加传染性,也不会导致免疫逃避,至少在本研究中采用的检测系统中是这样。我们的研究结果表明,Delta变异相对于Kappa变异的全球优势可能归因于其优越的传染性和传播性,而不是增强的免疫逃避能力。这些结果为刺突蛋白突变的功能后果提供了有价值的见解,并可能有助于预测未来SARS-CoV-2变体的出现和传播。这种理解对于加强公共卫生准备和为下一代疫苗和疗法的开发提供信息至关重要。
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来源期刊
Journal of microbiology and biotechnology
Journal of microbiology and biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-MICROBIOLOGY
CiteScore
5.50
自引率
3.60%
发文量
151
审稿时长
2 months
期刊介绍: The Journal of Microbiology and Biotechnology (JMB) is a monthly international journal devoted to the advancement and dissemination of scientific knowledge pertaining to microbiology, biotechnology, and related academic disciplines. It covers various scientific and technological aspects of Molecular and Cellular Microbiology, Environmental Microbiology and Biotechnology, Food Biotechnology, and Biotechnology and Bioengineering (subcategories are listed below). Launched in March 1991, the JMB is published by the Korean Society for Microbiology and Biotechnology (KMB) and distributed worldwide.
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