Skip to Main content Skip to Navigation
New interface
Journal articles

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.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03861292
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

Links full text

Identifiers

Citation

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⟩

Share

Metrics

Record views

0