Published June 25, 2024 | Version Published
Journal Article Open

Human antibodies in Mexico and Brazil neutralizing tick-borne flaviviruses

Abstract

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.

Copyright and License

© 2024 The Author(s). Published by Elsevier Under a Creative Commons license.

Acknowledgement

We thank all study participants as well as the clinical and research teams at Columbia University (New York), The Oswaldo Cruz Foundation (Brazil), and the National Institute of Respiratory Diseases (Mexico). We thank Ted Pierson (NIH) for providing the plasmids pZIKV-HPF-CprME and pWNVII-Rep-REN-IB, Pei Yong Shi for providing pFLWNV, and Aaron Brault (CDC) for providing the DTV 2-plasmid infectious clone system prior to publication. We thank Andrea Celoria for technical assistance, William Schneider for assistance in viral RNA sequencing, and Kristie Gordon for fluorescence-activated cell sorting. We thank Alison Ashbrook for POWV stock genome copy determinations and Tyler Lewy for providing the WNV NY99 virus stock. The graphical abstract was prepared with BioRender. This work was supported in part by the Swiss Vaccine Research Institute (SVRI) and by a Czech-Swiss collaborative project funded jointly by the Czech Science Foundation (no. GF21-05445L to D.R.) and the Swiss National Science Foundation (no. 310030L_196866 to D.F.R.) and NIH grants U01 AI151698 (United World Antiviral Research Network [UWARN] to M.C.N. and D.F.R.); P01 AI138938 and U19 AI111825 (to C.M.R., M.C.N., P.J.B., D.F.R.); R01 AI052473R01 TW009504, and R01 AI174105 (to A.I.K.); and R21 AI142010 (to M.R.M.). The study was also possible thanks to the IRB-Rockefeller University Stavros Niarchos Foundation Partnership for Global Infectious Disease Research supported by the Fondazione Leonardo and was supported in part by a pilot project award (to M.R.M) through grant no. UL1TR001866 from the National Center for Advancing Translational Sciences (NCATS, NIH Clinical and Translational Science Award [CTSA] program), and the Mexican government (Programa Presupuestal P016Anexo 13 del Decreto del Presupuesto de Egresos de la Federación). M.C.N. is a Howard Hughes Medical Institute (HHMI) Investigator. This article is subject to HHMI’s open access to publications policy. HHMI lab heads have previously granted a non-exclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication.

Contributions

T.C.R., T.K., J.R.K., L.S., H.-H.H., M.A., A.J., A.P., Y.E.L., A.G., F.G., J.C., B.C., F.B., E.T., and P.S. produced reagents, performed experiments, and analyzed the data; L.S. and S.G.M. performed computational structural and sequence analyses; M.G.R., F.C., A.I.K., B.A.F., S.A.-R., and G.R.-T. provided human samples; C.M.R., M.C.N., P.J.B., D.R., and L.V. supervised portions of the work; J.R.K., M.R.M., and D.F.R. conceived the study, coordinated and supervised the execution, analyzed the data, and wrote the manuscript, with contributions by the other authors.

Data Availability

Document S1. Figures S1–S4

able S1. POWV-EDIII antibody sequences, related to Figure 2

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Additional details

Funding

Swiss Vaccine Research Institute
Czech Science Foundation
GF21-05445L
Swiss National Science Foundation
310030L_196866
National Institutes of Health
U01 AI151698
National Institutes of Health
P01 AI138938
National Institutes of Health
U19 AI111825
National Institutes of Health
R01 AI052473
National Institutes of Health
R01 TW009504
National Institutes of Health
R01 AI174105
National Institutes of Health
R21 AI142010
Stavros Niarchos Foundation
Rockefeller University
Institute for Research in Biomedicine
National Institutes of Health
UL1TR001866
Howard Hughes Medical Institute

Caltech Custom Metadata

Caltech groups
Division of Biology and Biological Engineering (BBE), Richard N. Merkin Institute for Translational Research