@article{40674dafccc84bf49673fd313c75ec8a,
title = "Impact of prior dengue virus infection on Zika virus infection during pregnancy in marmosets",
abstract = "Zika virus (ZIKV) infection during pregnancy causes severe developmental defects in newborns, termed congenital Zika syndrome (CZS). Factors contributing to a surge in ZIKV-associated CZS are poorly understood. One possibility is that ZIKV may exploit the antibody-dependent enhancement of infection mechanism, mediated by cross-reactive antibodies from prior dengue virus (DENV) infection, which may exacerbate ZIKV infection during pregnancy. In this study, we investigated the impact of prior DENV infection or no DENV infection on ZIKV pathogenesis during pregnancy in a total of four female common marmosets with five or six fetuses per group. The results showed that negative-sense viral RNA copies increased in the placental and fetal tissues of DENV-immune dams but not in DENV-na{\"i}ve dams. In addition, viral proteins were prevalent in endothelial cells, macrophages, and neonatal Fc receptor–expressing cells in the placental trabeculae and in neuronal cells in the brains of fetuses from DENV-immune dams. DENV-immune marmosets maintained high titers of cross-reactive ZIKV-binding antibodies that were poorly neutralizing, raising the possibility that these antibodies might be involved in the exacerbation of ZIKV infection. These findings need to be verified in a larger study, and the mechanism involved in the exacerbation of ZIKV infection in DENV-immune marmosets needs further investigation. However, the results suggest a potential negative impact of preexisting DENV immunity on subsequent ZIKV infection during pregnancy in vivo.",
author = "Kim, {In Jeong} and Tighe, {Michael P.} and Clark, {Madeline J.} and Gromowski, {Gregory D.} and Lanthier, {Paula A.} and Travis, {Kelsey L.} and Bernacki, {Derek T.} and Cookenham, {Tres S.} and Lanzer, {Kathleen G.} and Szaba, {Frank M.} and Tamhankar, {Manasi A.} and Ross, {Corrina N.} and Tardif, {Suzette D.} and Donna Layne-Colon and Dick, {Edward J.} and Olga Gonzalez and {Giraldo Giraldo}, {Maria I.} and Patterson, {Jean L.} and Blackman, {Marcia A.}",
note = "Funding Information: Acknowledgments:W ethankT .EndyatCEPIforinitialhelpinconceptualizingthestudy, L.L.CoffeyattheUniversityofCalifornia,DavisforprovidingtheZIKV-BrazilSPH2015virus strain,andJ.BourneattheNationalInstituteofMentalHealthforconstructivediscussions.W e aregratefultotheveterinarytechniciansandmarmosetcarestaffatSNPRC,includingJ.Greig, C.Hinojosa,E.Morin,andA.Alvarezforassistancewiththemarmosettechnicalwork.Funding: ThisstudywassupportedbyinternalfundingfromTrudeauInstitute(TRN-UPS00)andNIH grant#P51OD011133awardedtotheSouthwestNationalPrimateCenteroftheT exas BiomedicalResearchInstitute.Marmosetpathologyworkreportedinthisstudywassupported bytheOfficeoftheDirector,theNationalInstitutesofHealth(grant#S10OD028732).Apartof the study was supported by research career development award K12HD052023, Building InterdisciplinaryResearchCareersinW omen's HealthProgram-BIRCWH;UTMB-IHIICIRWH 2022; and NIH/NIAID R01AI134907 awarded to M.I.G.G. The content is solely the responsibility oftheauthorsanddoesnotnecessarilyrepresenttheofficialviewsoftheNationalInstitutesof Health.Authorcontributions:M.A.B.,I.-J.K.,andJ.L.P .conceivedthestudy.M.A.B.andJ.L.P . obtainedfunding.K.G.L.,D.L.-C.,andC.N.R.coordinatedthestudyandsamplecollectionat T exasBiomedicalResearchInstitute.P .A.L. conductedserologyanalyses.M.J.C.andF .M.S. performedqRT-PCR.Theflowcytometry–basedADEassaywasperformedbyM.J.C.,T .S.C., and D.T .B. atTrudeauInstituteandbyG.D.G.atWRAIR.M.I.G.clonedmarmosetFcγR/CD64and preparedthepDNAconstruct.M.P .T ., K.L.T ., O.G.,andE.J.D.conductedhistopathologyand imaging.I.-J.K.performeddataanalysesandwrotetheoriginalmanuscript.M.A.B.,J.L.P ., C.N.R., and K.G.L. reviewed and edited the manuscript. All authors reviewed and approv ed the manuscript.Competinginterests:J.L.P .servesasapaidconsultantforFDADivisionof Toxicology.Theotherauthorsdeclarethattheyhavenocompetinginterests.Dataand materialsavailability:Alldataassociatedwiththisstudycanbefoundinthemaintextorthe SupplementaryMaterials.ThechimericantibodycloneZIKV-MAR(RRID,AB_2895628)is availablefromtheNHPReagentResource(R24OD028257).PlasmidDNAcontainingthegene encodingmarmosetFcγRisavailablefromM.I.G.underamaterialtransferagreementwiththe UniversityofT exasMedicalBranch–Galveston.Informationaboutallcommerciallyavailable reagents is pro vided in data file S2. Funding Information: We thank T. Endy at CEPI for initial help in conceptualizing the study, L. L. Coffey at the University of California, Davis for providing the ZIKV-Brazil SPH2015 virus strain, and J. Bourne at the National Institute of Mental Health for constructive discussions. We are grateful to the veterinary technicians and marmoset care staff at SNPRC, including J. Greig, C. Hinojosa, E. Morin, and A. Alvarez for assistance with the marmoset technical work. This study was supported by internal funding from Trudeau Institute (TRN-UPS00) and NIH grant #P51OD011133 awarded to the Southwest National Primate Center of the Texas Biomedical Research Institute. Marmoset pathology work reported in this study was supported by the Office of the Director, the National Institutes of Health (grant #S10OD028732). A part of the study was supported by research career development award K12HD052023, Building Interdisciplinary Research Careers in Women's Health Program-BIRCWH; UTMB-IHII CIRWH 2022; and NIH/NIAID R01AI134907 awarded to M.I.G.G. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",
year = "2023",
doi = "10.1126/scitranslmed.abq6517",
language = "English (US)",
volume = "15",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "699",
}