A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity

Jose Angel Regla-Nava, Ying Ting Wang, Camila R. Fontes-Garfias, Yang Liu, Thasneem Syed, Mercylia Susantono, Andrew Gonzalez, Karla M. Viramontes, Shailendra Kumar Verma, Kenneth Kim, Sara Landeras-Bueno, Chun Teng Huang, Daniil M. Prigozhin, Joseph G. Gleeson, Alexey V. Terskikh, Pei Yong Shi, Sujan Shresta

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Zika virus (ZIKV) and dengue virus (DENV) are arthropod-borne pathogenic flaviviruses that co-circulate in many countries. To understand some of the pressures that influence ZIKV evolution, we mimic the natural transmission cycle by repeating serial passaging of ZIKV through cultured mosquito cells and either DENV-naive or DENV-immune mice. Compared with wild-type ZIKV, the strains passaged under both conditions exhibit increased pathogenesis in DENV-immune mice. Application of reverse genetics identifies an isoleucine-to-valine mutation (I39V) in the NS2B proteins of both passaged strains that confers enhanced fitness and escape from pre-existing DENV immunity. Introduction of I39V or I39T, a naturally occurring homologous mutation detected in recent ZIKV isolates, increases the replication of wild-type ZIKV in human neuronal precursor cells and laboratory-raised mosquitoes. Our data indicate that ZIKV strains with enhanced transmissibility and pathogenicity can emerge in DENV-naive or -immune settings, and that NS2B-I39 mutants may represent ZIKV variants of interest.

Original languageEnglish (US)
Article number110655
JournalCell Reports
Issue number2
StatePublished - Apr 12 2022


  • CP: Microbiology
  • Flavivirus evolution
  • cross-protective immunity
  • dengue virus
  • mouse-adapted virus
  • viral pathogenesis
  • viral transmission
  • viral variants
  • zika virus

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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