Kill or be killed: The epic battle between Zika virus and cells revealed

Protein-gene interactome map reveals how Zika virus overrides molecular machinery in human neurospheres. Zika virus (ZIKV) infection during pregnancy has been linked to an increase in the number of infants born with brain malformations in Brazil. Although many studies have confirmed the association between ZIKV infection and microcephaly, the underlying molecular pathways remain unclear, and currently there is no treatment for ZIKV. In particular, how ZIKV overrides cellular machineries to ensure its self-replication and how exactly the altered molecular pathways cause the failure of brain development need to be further investigated. In this new study, Garcez et al. reveal ZIKVs survival strategies and effects on the infected brain in molecular detail. They used transcriptomics and proteomics to examine the interactome map of proteins and genes altered in human stem cell-derived neurospheres by ZIKV infection. ZIKV up-regulates cellular proteins required for viral translation, which indicates that ZIKV hijacks proteins to support its replication. Simultaneously, ZIKV down-regulates proteins associated with cell cycle progression and neuronal differentiation to allow viral replication cycles. As a consequence, the cells deceived by ZIKV pay a high price. ZIKV-infected neurospheres have decreased numbers of neural progenitors and newborn neurons, and the proportion of cells containing damaged DNA is enriched. This suggests that cell death in both radial glia-like cells, which are capable of generating neurons and nonneuronal cells, as well as neural stem cells might be associated with damaged DNA. In summary, this study illustrates how the protein-gene interactome map of ZIKV-infected neurospheres can provide insights on identifying a wide range of target molecules and pathways affected by ZIKV. These results may help us better understand the underlying molecular mechanisms in ZIKV-induced microcephaly and may contribute to the development of therapeutic strategies.