Author(s): Koenig MR, Razo E, Mitzey A, Newman CM, Dudley DM, Breitbach ME, Semler MR, Stewart LM, Weiler AM, Rybarczyk S, Bach KM, Mohns MS, Simmons HA, Mejia A, Fritsch M, Dennis M, Teixeira LBC, Schotzko ML, Nork TM, Rasmussen CA, Katz A, Nair V, Hou J, Hartman A, Ver Hoeve J, Kim C, Schneider ML, Ausderau K, Kohn S, Jaeger AS, Aliota MT, Hayes JM, Schultz-Darken N, Eickhoff J, Antony KM, Noguchi K, Zeng X, Permar S, Prabhakaran V, Capuano S 3rd, Friedrich TC, Golos TG, O’Connor DH, Mohr EL. Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus. PLoS One. 2020 Oct 22;15(10):e0235877. doi: 10.1371/journal.pone.0235877. eCollection 2020. PMID 33091010
Journal: Plo S One, Volume 15, Issue 10, 2020
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.