Differential Neuronal Susceptibility and Apoptosis in Congenital Zika Virus Infection

To characterize the mechanism of Zika virus (ZIKV)-associated microcephaly, we performed immunolabeling on brain tissue from a 20-week fetus with intrauterine ZIKV infection. Although ZIKV demonstrated a wide range of neuronal and non-neuronal tropism, the infection rate was highest in intermediate progenitor cells and immature neurons. Apoptosis was observed in both infected and uninfected bystander cortical neurons, suggesting a role for paracrine factors in induction of neuronal apoptosis. Our results highlight differential neuronal susceptibility and neuronal apoptosis as potential mechanisms in the development of ZIKV-associated microcephaly, and may provide insights into the design and best timing of future therapy. Ann Neurol 2017;82:121-127.