Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 1624 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. / 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; Falkenstein, Kathrine P.; Kaur, Amitinder; Curry, Christine; Kallas, Esper G.; Desrosiers, Ronald Charles; Goldschmidt-Clermont, Pascal; Whitehead, Stephen S.; Andersen, Kristian G.; Bonaldo, Myrna C.; Lackner, Andrew A.; Panganiban, Antonito T.; Burton, Dennis R.; Watkins, David.
In: Nature Communications, Vol. 9, No. 1, 1624, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques
AU - Magnani, Diogo M.
AU - Rogers, Thomas F.
AU - Maness, Nicholas J.
AU - Grubaugh, Nathan D.
AU - Beutler, Nathan
AU - Bailey, Varian K.
AU - Gonzalez-Nieto, Lucas
AU - Gutman, Martin J.
AU - Pedreño-Lopez, Núria
AU - Kwal, Jaclyn M.
AU - Ricciardi, Michael J.
AU - Myers, Tereance A.
AU - Julander, Justin G.
AU - Bohm, Rudolf P.
AU - Gilbert, Margaret H.
AU - Schiro, Faith
AU - Aye, Pyone P.
AU - Blair, Robert V.
AU - Martins, Mauricio
AU - Falkenstein, Kathrine P.
AU - Kaur, Amitinder
AU - Curry, Christine
AU - Kallas, Esper G.
AU - Desrosiers, Ronald Charles
AU - Goldschmidt-Clermont, Pascal
AU - Whitehead, Stephen S.
AU - Andersen, Kristian G.
AU - Bonaldo, Myrna C.
AU - Lackner, Andrew A.
AU - Panganiban, Antonito T.
AU - Burton, Dennis R.
AU - Watkins, David
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85045999099&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04056-4
DO - 10.1038/s41467-018-04056-4
M3 - Article
C2 - 29691387
AN - SCOPUS:85045999099
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1624
ER -