RT Journal Article
SR Electronic
T1 Maternal immunity and antibodies to dengue virus promote infection and Zika virus–induced microcephaly in fetuses
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaav3208
DO 10.1126/sciadv.aav3208
VO 5
IS 2
A1 Rathore, Abhay P. S.
A1 Saron, Wilfried A. A.
A1 Lim, Ting
A1 Jahan, Nusrat
A1 St. John, Ashley L.
YR 2019
UL http://advances.sciencemag.org/content/5/2/eaav3208.abstract
AB Zika virus (ZIKV), an emergent flaviviral pathogen, has been linked to microcephaly in neonates. Although the risk is greatest during the first trimester of pregnancy in humans, timing alone cannot explain why maternal ZIKV infection leads to severe microcephaly in some fetuses, but not others. The antigenic similarities between ZIKV and dengue virus (DENV), combined with high levels of DENV immunity among ZIKV target populations in recent outbreaks, suggest that anti-DENV maternal antibodies could promote ZIKV-induced microcephaly. We demonstrated maternal-to-fetal ZIKV transmission, fetal infection, and disproportionate microcephaly in immunocompetent mice. We show that DENV-specific antibodies in ZIKV-infected pregnant mice enhance vertical ZIKV transmission and result in a severe microcephaly-like syndrome, which was dependent on the neonatal Fc receptor, FcRN. This novel immune-mediated mechanism of vertical transmission of viral infection is of special concern because ZIKV epidemic regions are also endemic to DENV.