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

Bae Sojung|Myoung Jinjong|Kim Tae-Hun
한국미생물·생명공학회 (The Korean Society For Microbiology And Biotechnology)|2024.12|Journal of Microbiology and Biotechnology|제34권 제12호|pp. 2506-2515|DOI 10.4014/jmb.2411.11001

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키워드

SARS-CoV-2infectivityimmune evasion
주제분류생물학

초록

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 SARSCoV-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.

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 SARSCoV-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.

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관련 논문AI추천

Domain-Specific Impacts of Spike Protein Mutations on Infectivity and Antibody Escape in SARS-CoV-2 Omicron BA.1Bae Sojung, Kim Tae-Hun, Myoung Jinjong한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta VariantBae Sojung, Goo Sunggeun, Kim Tae-Hun, Myoung Jinjong한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2023 · 제33권 제12호SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene김수현, 박호영, 송창선, 전현정, Hisham Yasmin대한면역학회 · Immune Network2021 · 제21권 제5호SARS-CoV-2 Omicron Variant of Concern: Everything You Wanted to Know about Omicron but Were Afraid to Ask최준용, Davey M. Smith, Dong Hoon Shin연세대학교의과대학 · Yonsei Medical Journal2022 · 제63권 제11호SARS-CoV-2 Antibody Neutralization Assay Platforms Based on Epitopes Sources: Live Virus, Pseudovirus, and Recombinant S Glycoprotein RBDAnam Khairul, Prasetyaningrum Pekik Wiji, Santoso Adi, Septisetyani Endah Puji대한면역학회 · Immune Network2021 · 제21권 제6호SARS-CoV-2 Variants of Concern최준용, Davey M. Smith연세대학교의과대학 · Yonsei Medical Journal2021 · 제62권 제11호

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