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

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English (US)
Article number	110655
Journal	Cell Reports
Volume	39
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2022.110655
State	Published - Apr 12 2022

Keywords

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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Regla-Nava, J. A., Wang, Y. T., Fontes-Garfias, C. R., Liu, Y., Syed, T., Susantono, M., Gonzalez, A., Viramontes, K. M., Verma, S. K., Kim, K., Landeras-Bueno, S., Huang, C. T., Prigozhin, D. M., Gleeson, J. G., Terskikh, A. V., Shi, P. Y., & Shresta, S. (2022). A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity. Cell Reports, 39(2), Article 110655. https://doi.org/10.1016/j.celrep.2022.110655

Regla-Nava, JA, Wang, YT, Fontes-Garfias, CR, Liu, Y, Syed, T, Susantono, M, Gonzalez, A, Viramontes, KM, Verma, SK, Kim, K, Landeras-Bueno, S, Huang, CT, Prigozhin, DM, Gleeson, JG, Terskikh, AV, Shi, PY & Shresta, S 2022, 'A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity', Cell Reports, vol. 39, no. 2, 110655. https://doi.org/10.1016/j.celrep.2022.110655

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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.",

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AU - Regla-Nava, Jose Angel

AU - Wang, Ying Ting

AU - Fontes-Garfias, Camila R.

AU - Liu, Yang

AU - Syed, Thasneem

AU - Susantono, Mercylia

AU - Gonzalez, Andrew

AU - Viramontes, Karla M.

AU - Verma, Shailendra Kumar

AU - Kim, Kenneth

AU - Landeras-Bueno, Sara

AU - Huang, Chun Teng

AU - Prigozhin, Daniil M.

AU - Gleeson, Joseph G.

AU - Terskikh, Alexey V.

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AU - Shresta, Sujan

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N2 - 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.

AB - 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.

KW - CP: Microbiology

KW - Flavivirus evolution

KW - cross-protective immunity

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KW - mouse-adapted virus

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

Abstract

Keywords

ASJC Scopus subject areas

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