Abstract
Malformations of the fetal CNS, known as microcephaly, have been linked to Zika virus (ZIKV) infection. Here, the responses of mammalian and mosquito cell lines, in addition to primary human fetal astrocytes and neurons were studied following infection by ZIKV strains Brazil 2016 (ZIKV-BR), French Polynesia 2013 (ZIKV-FP), and Uganda #976 1947 (ZIKV-UG). Viral production, cell viability, infectivity rate, and mobility of endocytotic ZIKV-laden vesicles were compared. All cell types (SK-N-SH, Vero E6, C6/36, human fetal astrocytes and human fetal neurons) released productive virus. Among primary cells, astrocytes were more susceptible to ZIKV infection than neurons, released more progeny virus and tolerated higher virus loads than neurons. In general, the infection rate of ZIKV-UG strain was the highest. All ZIKV strains elicited differences in trafficking of ZIKV-laden endocytotic vesicles in the majority of cell types, including astrocytes and neurons, except in mosquito cells, where ZIKV infection failed to induce cell death. These results represent a thorough screening of cell viability, infection and production of three ZIKV strains in five different cell types and demonstrate that ZIKV affects vesicle mobility in all but mosquito cells.
Highlights
Growth of the fetal cerebral cortex continues throughout fetal development, but at the mid-gestation period extensive neurogenesis and gliogenesis occur[15,16,17,18]
We used two Asian-lineage Zika virus (ZIKV) strains ZIKV-FP (2013) and ZIKV strains Brazil 2016 (ZIKV-BR) (2016), which are responsible for the latest international outbreaks causing neuropathology[13], and the African lineage ZIKV-UG #976 (1947), to test their infectivity rate, release, effects on cell viability, cytopathologic effects (CPE), and the mobility of ZIKV-laden endocytotic vesicles in mammalian (SK-N-SH and Vero E6) and mosquito (C6/36) cell lines, as well as in human fetal astrocytes and neurons
Productive ZIKV replication of strains ZIKV-BR and ZIKV-UG in the form of released infectious virions was detected at 18 hpi, while the productive replication of ZIKV-FP was delayed in all cell lines (Fig. 1ai)
Summary
Growth of the fetal cerebral cortex continues throughout fetal development, but at the mid-gestation period extensive neurogenesis and gliogenesis occur[15,16,17,18]. At around gestation week (gw) 20, ZIKV-infected fetuses show severely hampered brain development, evident as a reduction in brain size[6] By this time, the astrocyte population is already abundant and their infection may contribute to further expansion of microcephaly, which may have originated in ZIKV infection of human neural progenitor cells (NPCs), neural stem cells (NSC), www.nature.com/scientificreports/. We report how human astrocytes respond to ZIKV infection in terms of the extent of viral infection, release of productive virus, host cell survival, and intracellular traffic of ZIKV-laden endocytotic vesicles. We compared their responses to neurons and to selected mammalian and mosquito cell lines
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