Zika virus (ZIKV) is a re-emerged flavivirus transmitted by Aedes spp mosquitoes that has caused outbreaks of fever and rash on islands in the Pacific and in the Americas. These outbreaks have been associated with neurologic complications that include congenital abnormalities and Guillain-Barré syndrome (GBS). The pathogenesis of ZIKV-associated GBS, a potentially life-threatening peripheral nerve disease, remains unclear. Because Schwann cells (SCs) play a central role in peripheral nerve function and can be the target for damage in GBS, we characterized the interactions of ZIKV isolates from Africa, Asia and Brazil with human SCs in comparison with the related mosquito-transmitted flaviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2). SCs supported sustained replication of ZIKV and YFV, but not DENV. ZIKV infection induced increased SC expression of IL-6, interferon (IFN)β1, IFN-λ, IFIT-1, TNFα and IL-23A mRNAs as well as IFN-λ receptors and negative regulators of IFN signaling. SCs expressed baseline mRNAs for multiple potential flavivirus receptors and levels did not change after ZIKV infection. SCs did not express detectable levels of cell surface Fcγ receptors. This study demonstrates the susceptibility and biological responses of SCs to ZIKV infection of potential importance for the pathogenesis of ZIKV-associated GBS.
Conflict of interest statement
G.D. and R.A. declare no competing interests. D.E.G. is a member of the Takeda Zika virus vaccine data monitoring committee.
Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism.J Virol. 2019 Jun 28;93(14):e00151-19. doi: 10.1128/JVI.00151-19. Print 2019 Jul 15. J Virol. 2019. PMID: 31043530 Free PMC article.
Zika Virus Infects Human Sertoli Cells and Modulates the Integrity of the In Vitro Blood-Testis Barrier Model.J Virol. 2017 Oct 27;91(22):e00623-17. doi: 10.1128/JVI.00623-17. Print 2017 Nov 15. J Virol. 2017. PMID: 28878076 Free PMC article.
Experimental Zika virus infection in Aedes aegypti: Susceptibility, transmission & co-infection with dengue & chikungunya viruses.Indian J Med Res. 2018 Jan;147(1):88-96. doi: 10.4103/ijmr.IJMR_1142_17. Indian J Med Res. 2018. PMID: 29749366 Free PMC article.
Zika virus: Report from the task force on tropical diseases by the world Federation of Societies of intensive and critical care medicine.J Crit Care. 2018 Aug;46:106-109. doi: 10.1016/j.jcrc.2018.03.030. Epub 2018 Apr 5. J Crit Care. 2018. PMID: 29779827 Review.
Zika virus: An emerging flavivirus.J Microbiol. 2017 Mar;55(3):204-219. doi: 10.1007/s12275-017-7063-6. Epub 2017 Feb 28. J Microbiol. 2017. PMID: 28243937 Review.
Cited by 2 articles
Zika virus infection causes temporary paralysis in adult mice with motor neuron synaptic retraction and evidence for proximal peripheral neuropathy.Sci Rep. 2019 Dec 20;9(1):19531. doi: 10.1038/s41598-019-55717-3. Sci Rep. 2019. PMID: 31862897 Free PMC article.
Disease Resurgence, Production Capability Issues and Safety Concerns in the Context of an Aging Population: Is There a Need for a New Yellow Fever Vaccine?Vaccines (Basel). 2019 Nov 8;7(4):179. doi: 10.3390/vaccines7040179. Vaccines (Basel). 2019. PMID: 31717289 Free PMC article. Review.