Neonatal development in prenatally zika virus-exposed infant macaques with dengue immunity

Karla Ausderau, Sabrina Kabakov, Elaina Razo, Ann M. Mitzey, Kathryn M. Bach, Chelsea M. Crooks, Natalie Dulaney, Logan Keding, Cristhian Salas-Quinchucua, Lex G. Medina-Magües, Andrea M. Weiler, Mason Bliss, Jens Eickhoff, Heather A. Simmons, Andres Mejia, Kathleen M. Antony, Terry Morgan, Saverio Capuano, Mary L. Schneider, Matthew T. AliotaThomas C. Friedrich, David H. O’connor, Thaddeus G. Golos, Emma L. Mohr

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

Original languageEnglish (US)
Article number1878
JournalViruses
Volume13
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
Funding: This study was supported by the National Institutes of Health: P01 AI132132 (DHO), R01 AI138647 (DHO), R01 AI116382-01A1S1 (DHO), K08 AI139341 (ELM), R01 AI132563 (MTA and TCF), R01 AAH9849 (ELM and KA).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Macaque model
  • Maternal DENV infection
  • Neurodevelopment
  • Prenatal ZIKV exposure

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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