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Adaptation to host cell environment during experimental evolution of Zika virus

Abstract : Abstract 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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Contributor : Bastien Boussau Connect in order to contact the contributor
Submitted on : Saturday, November 19, 2022 - 5:06:46 PM
Last modification on : Sunday, November 20, 2022 - 3:49:41 AM

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Vincent Grass, Emilie Hardy, Kassian Kobert, Soheil Rastgou Talemi, Elodie Décembre, et al.. Adaptation to host cell environment during experimental evolution of Zika virus. Communications Biology, 2022, 5 (1), pp.1115. ⟨10.1038/s42003-022-03902-y⟩. ⟨hal-03861292⟩



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