Quantitative neuroanatomical analyses of Zika-exposed macaque brains

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Project Summary/Abstract While the devastating neural consequences (e.g., microcephaly) of fetal ZIKV infection are clear, the neural mechanisms that create those outcomes are not clear. Accumulating research from human cell lines and mice suggest that ZIKV's ability to infect neural progenitors may be one mechanism, but the extent to which these processes impact neuroanatomy in whole organisms and in primate (including human) brains are unknown. The proposed work takes the first step in understanding how ZIKV disrupts brain structure and function by performing whole-brain neuroanatomical analyses on brains from nonhuman primates infected with or exposed to ZIKV. We capitalize upon an already existing NIH-funded resource – the brains and other biological samples from rhesus macaques exposed to or infected with ZIKV as part of ongoing work establishing the rhesus macaque as a model for human ZIKV infection and testing vaccines for ZIKV. We will quantify the number, density, and cell size of neurons, glia, and dividing cells in a number of representative cortical and subcortical areas in macaques exposed to or infected with ZIKV at various times of fetal development or in adulthood. The overarching goal of the proposed work is to develop an understanding of how the timing of ZIKV infection relative to development and subsequent manifestation of ZIKV both in terms of clinical symptoms (fever, weight loss) and viremia (magnitude of infection, time of active infection) influence disruption of normal central nervous system neuroanatomy.