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
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.
