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Basic Characteristics of Mutations
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Mutation Site
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S455L |
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Mutation Site Sentence
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We functionally validated S455L, a substitution in ZIKV envelope (E) protein, recapitulating the adapted phenotype. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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E |
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Standardized Encoding Gene
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envelope
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Genotype/Subtype
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- |
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Viral Reference
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KX197192
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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TLR3
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Brazil |
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Literature Information
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PMID
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36271143
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Title
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Adaptation to host cell environment during experimental evolution of Zika virus
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Author
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Grass V,Hardy E,Kobert K,Talemi SR,Decembre E,Guy C,Markov PV,Kohl A,Paris M,Bockmann A,Munoz-Gonzalez S,Sherry L,Hofer T,Boussau B,Dreux M
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Journal
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Communications biology
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Journal Info
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2022 Oct 21;5(1):1115
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Abstract
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Zika virus (ZIKV) infection can cause important developmental and neurological defects in Humans. Type I/III interferon responses control ZIKV infection and pathological processes, yet the virus has evolved various mechanisms to defeat these host responses. Here, we established a pipeline to delineate at high-resolution the genetic evolution of ZIKV in a controlled host cell environment. We uncovered that serially passaged ZIKV acquired increased infectivity and simultaneously developed a resistance to TLR3-induced restriction. We built a mathematical model that suggests that the increased infectivity is due to a reduced time-lag between infection and viral replication. We found that this adaptation is cell-type specific, suggesting that different cell environments may drive viral evolution along different routes. Deep-sequencing of ZIKV populations pinpointed mutations whose increased frequencies temporally coincide with the acquisition of the adapted phenotype. We functionally validated S455L, a substitution in ZIKV envelope (E) protein, recapitulating the adapted phenotype. Its positioning on the E structure suggests a putative function in protein refolding/stability. Taken together, our results uncovered ZIKV adaptations to the cellular environment leading to accelerated replication onset coupled with resistance to TLR3-induced antiviral response. Our work provides insights into Zika virus adaptation to host cells and immune escape mechanisms.
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Sequence Data
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-
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