@article{343c82e5b3d54e40ac59c1e96691c2ef,
title = "A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity",
abstract = "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.",
keywords = "CP: Microbiology, Flavivirus evolution, cross-protective immunity, dengue virus, mouse-adapted virus, viral pathogenesis, viral transmission, viral variants, zika virus",
author = "Regla-Nava, {Jose Angel} and Wang, {Ying Ting} and Fontes-Garfias, {Camila R.} and Yang Liu and Thasneem Syed and Mercylia Susantono and Andrew Gonzalez and Viramontes, {Karla M.} and Verma, {Shailendra Kumar} and Kenneth Kim and Sara Landeras-Bueno and Huang, {Chun Teng} and Prigozhin, {Daniil M.} and Gleeson, {Joseph G.} and Terskikh, {Alexey V.} and Shi, {Pei Yong} and Sujan Shresta",
note = "Funding Information: This study was supported by grants from the National Institutes of Health (R01 AI153500 , R01 AI163188 , R56 AI148635 , and U01 AI151810 to S.S.; R01 NS106387 to J.G.G.; R01 AI134907 , R43 AI145617 , and UL1 TR001439 to P.-Y.S.) and from the Sealy & Smith Foundation , the Kleberg Foundation , the John S. Dunn Foundation , the Amon G. Carter Foundation , the Gilson Longenbaugh Foundation , and the Summerfield Robert Foundation to P.-Y.S. Funding Information: This study was supported by grants from the National Institutes of Health (R01 AI153500, R01 AI163188, R56 AI148635, and U01 AI151810 to S.S.; R01 NS106387 to J.G.G.; R01 AI134907, R43 AI145617, and UL1 TR001439 to P.-Y.S.) and from the Sealy & Smith Foundation, the Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gilson Longenbaugh Foundation, and the Summerfield Robert Foundation to P.-Y.S. J.A.R.-N. and S.S. conceived the project. J.A.R.-N. Y.-T.W. C.R.F.-G. Y.L. C.-T.H. T.S. M.S. A.G. K.M.V. S.V. K.K. D.M.P. and S.L. performed the experiments and analyzed the data. J.G.G. A.V.T. P.-Y.S. and S.S. obtained funding and designed the experiments. S.S. supervised the research. S.S. wrote the manuscript and other authors provided editorial comments. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = apr,
day = "12",
doi = "10.1016/j.celrep.2022.110655",
language = "English (US)",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}