Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for RNA Replication and Restricted for Immune Evasion

Journal of Virology
Benjamin O FultonMatthew J Evans

Abstract

The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the ZIKV MR766 genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle. The ZIKV structural genes showed the highest degree of insertional tolerance. Although the envelope (E) protein exhibited particular flexibility, the highly conserved envelope domain II (EDII) fusion loop of the E protein was intolerant of transposon insertions. The fusion loop is also a target of pan-flavivirus antibodies that are generated against other flaviviruses and neutralize a broad range of dengue virus and ZIKV isolates. The genetic restrictions identified within the epitopes in the EDII fusion loop likely explain the sequence and antigenic conservation of these regions in ZIKV and among multiple flaviviruses. Thus, our results ...Continue Reading

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Citations

Jan 13, 2018·Journal of Virology·Jeffrey W PerryAndrew W Tai
Nov 3, 2017·Journal of Virology·Tomokazu TamuraYoshiharu Matsuura
Dec 24, 2019·The Journal of Cell Biology·Yali CiLei Shi
Jul 19, 2019·Journal of Virology·Dagmara SzkolnickaDarius Moradpour
Aug 30, 2019·Journal of Virology·Tomokazu TamuraYoshiharu Matsuura
Sep 15, 2018·Bio-protocol·Jeffrey W Perry, Andrew W Tai
Mar 7, 2019·International Journal of Molecular Sciences·Jae Kyung Lee, Ok Sarah Shin
Oct 21, 2020·Emerging Microbes & Infections·Zhong LiHongmin Li
Apr 14, 2020·Computational and Structural Biotechnology Journal·Anel MahmutovicSören Abel
Jun 3, 2021·Viruses·Thomas D Burton, Nicholas S Eyre

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