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. Aliota; Thomas C. Friedrich; David H. O’Connor; Thaddeus G. Golos; Emma L. Mohr

doi:10.3390/v13091878

Viruses (Sep 2021)

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. Aliota,
Thomas C. Friedrich,
David H. O’Connor,
Thaddeus G. Golos,
Emma L. Mohr

Affiliations

Karla Ausderau: Department of Kinesiology, Occupational Therapy Program, University of Wisconsin–Madison, Madison, WI 53706, USA
Sabrina Kabakov: Department of Kinesiology, Occupational Therapy Program, University of Wisconsin–Madison, Madison, WI 53706, USA
Elaina Razo: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53792, USA
Ann M. Mitzey: Department of Comparative Biosciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Kathryn M. Bach: Department of Kinesiology, Occupational Therapy Program, University of Wisconsin–Madison, Madison, WI 53706, USA
Chelsea M. Crooks: Department of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Natalie Dulaney: Department of Kinesiology, Occupational Therapy Program, University of Wisconsin–Madison, Madison, WI 53706, USA
Logan Keding: Department of Comparative Biosciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Cristhian Salas-Quinchucua: Department of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Lex G. Medina-Magües: Department of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Andrea M. Weiler: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Mason Bliss: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Jens Eickhoff: Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison, WI 53792, USA
Heather A. Simmons: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Andres Mejia: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Kathleen M. Antony: Department of Obstetrics and Gynecology, University of Wisconsin–Madison, Madison, WI 53705, USA
Terry Morgan: Center for Developmental Health, Department of Obstetrics and Gynecology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 97239, USA
Saverio Capuano: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Mary L. Schneider: Department of Kinesiology, Occupational Therapy Program, University of Wisconsin–Madison, Madison, WI 53706, USA
Matthew T. Aliota: Department of Veterinary and Biomedical Sciences, University of Minnesota, Minneapolis, MN 55108, USA
Thomas C. Friedrich: Department of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI 53706, USA
David H. O’Connor: Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53715, USA
Thaddeus G. Golos: Department of Comparative Biosciences, University of Wisconsin–Madison, Madison, WI 53706, USA
Emma L. Mohr: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53792, USA

DOI: https://doi.org/10.3390/v13091878
Journal volume & issue: Vol. 13, no. 9
p. 1878

Abstract

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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.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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