TY - JOUR
T1 - Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus
AU - Koenig, Michelle R.
AU - Razo, Elaina
AU - Mitzey, Ann
AU - Newman, Christina M.
AU - Dudley, Dawn M.
AU - Breitbach, Meghan E.
AU - Semler, Matthew R.
AU - Stewart, Laurel M.
AU - Weiler, Andrea M.
AU - Rybarczyk, Sierra
AU - Bach, Kathryn M.
AU - Mohns, Mariel S.
AU - Simmons, Heather A.
AU - Mejia, Andres
AU - Fritsch, Michael
AU - Dennis, Maria
AU - Teixeira, Leandro B.C.
AU - Schotzko, Michele L.
AU - Michael Nork, T.
AU - Rasmussen, Carol A.
AU - Katz, Alex
AU - Nair, Veena
AU - Hou, Jiancheng
AU - Hartman, Amy
AU - Hoeve, James Ver
AU - Kim, Charlene
AU - Schneider, Mary L.
AU - Ausderau, Karla
AU - Kohn, Sarah
AU - Jaeger, Anna S.
AU - Aliota, Matthew T.
AU - Hayes, Jennifer M.
AU - Schultz-Darken, Nancy
AU - Eickhoff, Jens
AU - Antony, Kathleen M.
AU - Noguchi, Kevin
AU - Zeng, Xiankun
AU - Permar, Sallie
AU - Prabhakaran, Vivek
AU - Capuano, Saverio
AU - Friedrich, Thomas C.
AU - Golos, Thaddeus G.
AU - O'Connor, David H.
AU - Mohr, Emma L.
N1 - Publisher Copyright:
© 2020 Public Library of Science. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.
AB - Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.
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U2 - 10.1371/journal.pone.0235877
DO - 10.1371/journal.pone.0235877
M3 - Article
C2 - 33091010
AN - SCOPUS:85094130445
SN - 1932-6203
VL - 15
JO - PloS one
JF - PloS one
IS - 10 October
M1 - e0235877
ER -