Characterizing the Cytopathogenicity of Zika Virus in Human Schwann Cells
Embargo until
Date
2018-04-27
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
Zika virus (ZIKV) is a newly reemerged RNA virus that belongs to the flavivirus genus of the family Flaviviridae. It is a mosquito-borne virus, transmitted mainly by the Aedes spp and was considered a relatively unimportant pathogen until a large outbreak in the Pacific Island of Yap in 2007, followed by outbreaks in the South Pacific, Caribbean and Americas in 2015. A systematic review of the Zika outbreaks found that ZIKV is a cause of congenital abnormalities and has been associated with an increase in cases of Guillain-Barré syndrome (GBS), a potentially life-threatening peripheral nerve disease characterized by rapidly progressive, symmetrical weakness of the extremities. The pathogenesis of GBS associated with ZIKV infection remains unclear, and therefore our study focused on human Schwann cells (hSCs) which play a central role in peripheral nerve function, maintenance and repair. Schwann cells ensheathe and myelinate axons of peripheral nerves by wrapping around the shaft of an individual peripheral axon.
Another major characteristic of the Zika outbreak in the 21st century was that it followed a similar geographic distribution as another flavivirus, Dengue (DENV). The cross-talk and epidemiological similarity between the two viruses leads to the possible role of antibody dependent enhancement (ADE) as a mechanism driving enhanced replication and more severe illness seen during the ZIKV emergency.
Our study revealed that three different strains of Zika virus (1968 Nigeria, 2014 Thailand and 2015 Brazil) can infect, induce cytopathic effect and replicate well in hSCs. The comparative infection with other flaviviruses like Dengue virus (NGC) and Yellow Fever virus (17D) showed that hSCs are more susceptible to ZIKV. ZIKV infection in hSCs led to the upregulation of proinflammatory cytokines, mRNAs for IL-6, IFNβ1, IFIT-1, TNF, and IL-23A were observed to be upregulated in ZIKV (Fortaleza) infected hSCs. As compared to Yellow Fever virus infected hSCs, ZIKV infected hSCs showed a robust type III interferon response (IL-29) with an increase in its receptor levels (IL-10RB and IFNLR1) and negative regulators (SOCS1/SOCS3). We found no evidence of ADE between DENV and ZIKV infection of hSCs. This study demonstrates the cytopathogenicity of ZIKV infection in peripheral nerve cells and helps to understand the biological properties potentially contributing to the development of Guillain-Barré syndrome.
Description
Keywords
Zika Virus, Human Schwann Cells, Guillain-Barré syndrome, Antibody Dependent Enhancement, Interferon Lambda