Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques ( Macaca mulatta ) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. T...

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Veröffentlicht in:Nature communications 2018-04, Vol.9 (1), p.1624-8, Article 1624
Hauptverfasser: Magnani, Diogo M., Rogers, Thomas F., Maness, Nicholas J., Grubaugh, Nathan D., Beutler, Nathan, Bailey, Varian K., Gonzalez-Nieto, Lucas, Gutman, Martin J., Pedreño-Lopez, Núria, Kwal, Jaclyn M., Ricciardi, Michael J., Myers, Tereance A., Julander, Justin G., Bohm, Rudolf P., Gilbert, Margaret H., Schiro, Faith, Aye, Pyone P., Blair, Robert V., Martins, Mauricio A., Falkenstein, Kathrine P., Kaur, Amitinder, Curry, Christine L., Kallas, Esper G., Desrosiers, Ronald C., Goldschmidt-Clermont, Pascal J., Whitehead, Stephen S., Andersen, Kristian G., Bonaldo, Myrna C., Lackner, Andrew A., Panganiban, Antonito T., Burton, Dennis R., Watkins, David I.
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Sprache:eng
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Zusammenfassung:Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques ( Macaca mulatta ) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission. Zika virus (ZIKV) infection in pregnant women has been associated with fetal developmental defects. Here, the authors show that a Brazilian ZIKV isolate causes fetal demise in non-human primates and that antibody treatment at time of peak viremia is insufficient to clear ZIKV replication from amniotic fluid.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-04056-4