A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity
- La Jolla Institute for Immunology, CA (United States); Univ. de Guadalajara (Mexico)
- La Jolla Institute for Immunology, CA (United States)
- University of Texas Medical Branch, Galveston, TX (United States)
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrative Bioimaging Division
- Univ. of California, San Diego, CA (United States)
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.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1893119
- Journal Information:
- Cell Reports, Journal Name: Cell Reports Journal Issue: 2 Vol. 39; ISSN 2211-1247
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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