ArticleJournal of virology2025
Deep mutationally scanned CHIKV E3/E2 virus library maps viral amino acid preferences and predicts viral escape mutants of neutralizing CHIKV antibodies.
Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Capsid inclusion in a CHIKV mRNA vaccine impairs adaptive immune responses.Cell reports. Medicine · 2026Article
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- In Silico Characterization of Conserved Epitopes in Alphavirus E2 Proteins: A Promising Approach for Pan-vaccine Design.ACS omega · 2025Article
- Deep mutational scanning and CRISPR-engineered viruses: tools for evolutionary and functional genomics studies.mSphere · 2025Review
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5 authors.
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Abstract
As outbreaks of chikungunya virus (CHIKV), a mosquito-borne alphavirus, continue to present public health challenges, additional research is needed to generate protective and safe vaccines and effective therapeutics. Prior research established a role for antibodies in mediating protection against CHIKV infection, and the early appearance of CHIKV-specific IgG or IgG neutralizing antibodies protects against progression to chronic CHIKV disease in humans. However, the importance of epitope specificity for these protective antibodies and how skewed responses contribute to the development of acute and chronic CHIKV-associated joint disease remains poorly understood. Here, we describe the deep mutational scanning of one of the dominant targets of neutralizing antibodies during CHIKV infection, the E3/E2 (also known as p62) glycoprotein complex, to simultaneously test thousands of p62 mutants against selective pressures of interest in a high throughput manner. Characterization of the virus library revealed achievement of high diversity while also selecting out nonfunctional virus variants. Furthermore, this study provides evidence that this virus library system can comprehensively map sites critical for the neutralization function of antibodies of both known and unknown p62 domain specificities.IMPORTANCEChikungunya virus (CHIKV) is a mosquito-borne alphavirus of global health concern that causes debilitating acute and chronic joint disease. Prior studies established a critical role for antibodies in protection against CHIKV infection. Here, we describe the generation of a high-throughput, functional virus library capable of identifying critical functional sites for anti-viral antibodies. This new tool can be used to better understand antibody responses associated with distinct CHIKV infection outcomes and could contribute to the development of efficacious vaccines and antibody-based therapeutics.
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