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Nat Microbiol. 2018 Feb;3(2):141-147. doi: 10.1038/s41564-017-0060-z. Epub 2017 Nov 20.

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. akiko.iwasaki@yale.edu.
4
Howard Hughes Medical Institute, Chevy Chase, MD, USA. akiko.iwasaki@yale.edu.

Abstract

Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly 1 and Guillain-Barré syndrome2,3 as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis 4 , meningoencephalitis 5 and fatal encephalitis 6 . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 -/- ) mice, an infection model that exhibits high viral burden within the central nervous system. We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1 deficiency in the haematopoietic compartment. However, spread of ZIKV within the central nervous system is supported by Ifnar1-deficient non-haematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood-brain barrier and a large influx of CD8+ effector T cells. We also find that antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV neuropathogenesis within a susceptible mouse model and suggests blood-brain barrier breakdown and T-cell-mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

PMID:
29158604
PMCID:
PMC5780207
DOI:
10.1038/s41564-017-0060-z
[Indexed for MEDLINE]
Free PMC Article

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