Adaptation to host cell environment during experimental evolution of Zika virus

Grass, V. et al. (2022) Adaptation to host cell environment during experimental evolution of Zika virus. Communications Biology, 5, 1115. (doi: 10.1038/s42003-022-03902-y) (PMID:36271143) (PMCID:PMC9587232)

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.

• Item Type: Articles
• Additional Information: This work was supported by grants from the “Agence Nationale pour la Recherche” (ANR-JCJC-EXAMIN), the “Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales” (ANRS-AO 2017-01), the European Union’s Horizon 2020 Research and innovation program under “ZIKALLIANCE” (Grant Agreement no. 734548) and FINOVI foundation (AO11) to M.D. The grants from “Fondation pour la recherche médicale” (contract Bioinformatic analysis for research in biology, DBI20141231313 and from the “Agence Nationale pour la Recherche” LabEx Ecofect (Grant ANR-11-LABX-0048) to M.D., B.B., and A.B.; A.K. is supported by the UK Medical Research Council (MC_UU_12014/8, MR/N017552/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kohl, Professor Alain
• Authors: Grass, V., Hardy, E., Kobert, K., Talemi, S. R., Décembre, E., Guy, C., Markov, P. V., Kohl, A., Paris, M., Böckmann, A., Muñoz-González, S., Sherry, L., Höfer, T., Boussau, B., and Dreux, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Communications Biology
• Publisher: Nature Research
• ISSN: 2399-3642
• ISSN (Online): 2399-3642
• Published Online: 21 October 2022
• Copyright Holders: Copyright © The Author(s) 2022
• First Published: First published in Communications Biology 5: 1115
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172630007		Arthropod-borne infections and emerging virus infections in high risk areas (Programme 4)	Alain Kohl	Medical Research Council (MRC)	MC_UU_12014/8	III - Centre for Virus Research
172580		The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategies	Alain Kohl	Medical Research Council (MRC)	MR/N017552/1	III-MRC-GU Centre for Virus Research