Abstract
Zika virus (ZIKV) is an emerging, mosquito-borne pathogen associated with a widespread 2015–2016 epidemic in the Western Hemisphere and a proven cause of microcephaly and other fetal brain defects in infants born to infected mothers. ZIKV infections have been also linked to other neurological illnesses in infected adults and children, including Guillain-Barré syndrome (GBS), acute flaccid paralysis (AFP) and meningoencephalitis, but the viral pathophysiology behind those conditions remains poorly understood. Here we investigated ZIKV infectivity in neuroblastoma SH-SY5Y cells, both undifferentiated and following differentiation with retinoic acid. We found that multiple ZIKV strains, representing both the prototype African and contemporary Asian epidemic lineages, were able to replicate in SH-SY5Y cells. Differentiation with resultant expression of mature neuron markers increased infectivity in these cells, and the extent of infectivity correlated with degree of differentiation. New viral particles in infected cells were visualized by electron microscopy and found to be primarily situated inside vesicles; overt damage to the Golgi apparatus was also observed. Enhanced ZIKV infectivity in a neural cell line following differentiation may contribute to viral neuropathogenesis in the developing or mature central nervous system.
Highlights
Several arthropod-borne flaviviruses are neuropathogenic to humans[1], including West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus, Powassan virus, and dengue virus[2,3,4]
Regular SH-SY5Y growing media contained 10% fetal bovine serum. Both protocols were successful in inducing differentiation, the more effective protocol was the addition of 10 μM retinoic acid (RA) for 2 days in 10% FBS media (Supplementary Fig. 2), which resulted in extensive production of neurites and formation of a stable monolayer (Supplementary Fig. 3A)
We report productive infection of neuroblastoma SH-SY5Y cells by multiple Zika virus (ZIKV) strains from the African and Asian lineages
Summary
Several arthropod-borne flaviviruses are neuropathogenic to humans[1], including West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus, Powassan virus, and dengue virus[2,3,4]. The susceptibility of human neuronal progenitor cells (NPCs) to ZIKV infection was demonstrated in in vitro studies of induced pluripotent stem cells[18] and with organoids and cortical neurospheres, which recapitulated the cell death, decrease in proliferation, and reduction of organoid volume that was seen in fetal tissues from microcephaly cases[19,20]. These studies demonstrated preferential ZIKV infection of progenitor stem cells, with only a minor percentage of mature neurons affected. DIFFERENTIATED day 0 plate cells infect differentiated cells differentiation treatment with 10 μM retinoic acid harvest cells at 48 hpi for viral IFA, plaque assay, and qRT-PCR
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
