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

doi:10.1016/j.celrep.2022.110655

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

Cell Rep. 2022 Apr 12;39(2):110655. doi: 10.1016/j.celrep.2022.110655.

Authors

Jose Angel Regla-Nava¹, Ying-Ting Wang¹, Camila R Fontes-Garfias², Yang Liu², Thasneem Syed¹, Mercylia Susantono¹, Andrew Gonzalez¹, Karla M Viramontes¹, Shailendra Kumar Verma¹, Kenneth Kim¹, Sara Landeras-Bueno¹, Chun-Teng Huang³, Daniil M Prigozhin⁴, Joseph G Gleeson⁵, Alexey V Terskikh³, Pei-Yong Shi⁶, Sujan Shresta⁷

Affiliations

¹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
² Department of Biochemistry and Molecular Biology, Sealy Institute for Drug Discovery, Department of Pharmacology and Toxicology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
³ Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
⁴ Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁵ Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
⁶ Department of Biochemistry and Molecular Biology, Sealy Institute for Drug Discovery, Department of Pharmacology and Toxicology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: peshi@utmb.edu.
⁷ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Electronic address: sujan@lji.org.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Cross Reactions
Dengue Virus* / genetics
Dengue*
Mice
Mutation / genetics
Zika Virus Infection*
Zika Virus* / genetics

Substances

Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding