Molecular determinants of Zika virus propagation and pathogenesis in human glial cells

All viruses require a host cell in which to grow and spread. Thus, all viruses make use of cellular processes, and these processes dictate whether a virus can successfully grow in any given cell. Arboviruses are viruses spread by arthropods, such as mosquitos. Zika virus (ZIKV) is a newly re-emerging arbovirus that has been identified as a public health threat by the World Health Organization. The mosquito that transmits ZIKV has been found in Canada, and climate change will make the mosquito and virus more prevalent. ZIKV causes birth defects and can have long-term effects in those children who survive infection. The severity of disease depends upon the age of the developing child, with most severe manifestations occurring during the first trimester of pregnancy, indicating age-related factors in ZIKV growth and pathology. Our prior global protein screens identified panels of cellular proteins that are common in ZIKV-susceptible cells, and others that are common in cells in which the virus cannot grow. We now seek to understand how a small number of these identified cellular genes and proteins cause their effects, and also at what stage during cell development these proteins switch from allowing ZIKV growth to inhibiting ZIKV growth.