{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Grass V"],"funding":["Medical Research Council"],"pagination":["1115"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9587232"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(1)"],"pubmed_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."],"journal":["Communications biology"],"pubmed_title":["Adaptation to host cell environment during experimental evolution of Zika virus."],"pmcid":["PMC9587232"],"funding_grant_id":["MC_UU_12014/8","MR/N017552/1"],"pubmed_authors":["Kohl A","Boussau B","Grass V","Markov PV","Paris M","Munoz-Gonzalez S","Sherry L","Talemi SR","Hardy E","Guy C","Dreux M","Decembre E","Hofer T","Kobert K","Bockmann A"],"additional_accession":[]},"is_claimable":false,"name":"Adaptation to host cell environment during experimental evolution of Zika virus.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-06-21T03:12:01.641Z","creation":"2025-04-19T22:47:25.584Z"},"accession":"S-EPMC9587232","cross_references":{"pubmed":["36271143"],"doi":["10.1038/s42003-022-03902-y"]}}