Spatial Coupling of Viral RNA Translation and Replication in Zika Infection

Abstract Zika virus (ZIKV), a mosquito-borne flavivirus, has emerged as a public health concern. Although asymptomatic or mild febrile illness in adults, ZIKV infection can lead to severe outcomes in pregnant women, including fetal microcephaly and congenital Zika syndrome. A hallmark of ZIKV pathogenesis is the virus-induced remodeling of the endoplasmic reticulum into specialized replication organelles (ROs), which function as spatially organized hubs that actively couple viral RNA synthesis with the host translation machinery. These specialized ROs enhance viral genome amplification, prioritizes viral mRNA translation, and minimizes the cytosolic exposure of immunostimulatory viral double-stranded RNA intermediates. This review explores how this spatial coupling underlies the unique tropism of ZIKV towards neural progenitor cells, a characteristic that sets it apart from other neurotropic flaviviruses. In particular, ZIKV adaptations that simultaneously promote viral replication and disrupt host neurogenesis are critically discussed.