ArticleNature communications2023
A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.Virologica Sinica · 2026Review
- ZIKV envelope protein is a strong blocker of early directional differentiation in the neural lineage.Communications biology · 2026Article
- Glycosylation of GETV E2 promotes pathogenesis in animal models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The modified mRNA vaccine protects immunocompromised AG129 mice from lethal challenge and multi-tissue infection by Zika virus.Emerging microbes & infections · 2025Article
- Zika virus inhibits cell death by inhibiting the expression of NLRP3 and A20.Journal of virology · 2025Article
- Distinct ZIKV strain signatures and type I IFN modulation reveal a protective role of brain endothelial interferon signalingFrontiers in cellular and infection microbiology · 2025Article
- Natural mutations in key NLS amino acids regulate nucleoplasmic shuttling and replication efficiency in PRRSV.Frontiers in microbiology · 2025Article
- The genetic and proliferation characterization analysis of novel coxsackievirus A12 in Beijing, China.Frontiers in microbiology · 2025Article
- An accumulated mutation gained in mosquito cells enhances Zika virus virulence and fitness in mice.Journal of virology · 2024Article
- The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.Molecular biomedicine · 2024Article
- Article
- Zika Virus-A Reemerging Neurotropic Arbovirus Associated with Adverse Pregnancy Outcomes and Neuropathogenesis.Pathogens (Basel, Switzerland) · 2024Review
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence shows the African lineage Zika virus (ZIKV) displays a more severe neurovirulence compared to the Asian ZIKV. However, viral determinants and the underlying mechanisms of enhanced virulence phenotype remain largely unknown. Herein, we identify a panel of amino acid substitutions that are unique to the African lineage of ZIKVs compared to the Asian lineage by phylogenetic analysis and sequence alignment. We then utilize reverse genetic technology to generate recombinant ZIKVs incorporating these lineage-specific substitutions based on an infectious cDNA clone of Asian ZIKV. Through in vitro characterization, we discover a mutant virus with a lysine to arginine substitution at position 101 of capsid (C) protein (termed K101R) displays a larger plaque phenotype, and replicates more efficiently in various cell lines. Moreover, K101R replicates more efficiently in mouse brains and induces stronger inflammatory responses than the wild type (WT) virus in neonatal mice. Finally, a combined analysis reveals the K101R substitution promotes the production of mature C protein without affecting its binding to viral RNA. Our study identifies the role of K101R substitution in the C protein in contributing to the enhanced virulent phenotype of the African lineage ZIKV, which expands our understanding of the complexity of ZIKV proteins.
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