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Updated: Feb 18, 2026
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice
Kellie A Jurado1, Laura J Yockey1, Patrick W Wong1
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
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.
Insights
Zika virus (ZIKV) causes neurological issues. In Ifnar1 knockout mice, ZIKV spreads to the brain, leading to paralysis via T-cell responses and blood-brain barrier breakdown.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Zika virus (ZIKV) is an emerging mosquito-borne RNA virus linked to severe neurological complications like microcephaly and Guillain-Barré syndrome.
- Previous research indicates other neurological manifestations including myelitis, meningoencephalitis, and encephalitis associated with ZIKV.
Purpose of the Study:
- To investigate the neuropathogenesis of ZIKV infection in type I interferon receptor (IFNAR) knockout (Ifnar1-/-) mice.
- To elucidate the mechanisms of ZIKV spread within the central nervous system (CNS) and its interaction with host immune cells.
Main Methods:
- Utilized Ifnar1-/- mice to model ZIKV infection with high CNS viral burden.
- Analyzed the role of hematopoietic and non-hematopoietic Ifnar1 deficiency in ZIKV systemic spread and CNS dissemination.
- Investigated the impact of ZIKV infection on astrocytes, blood-brain barrier integrity, and CD8+ T cell infiltration.
Main Results:
- Systemic ZIKV spread to the brain was dependent on Ifnar1 deficiency in hematopoietic cells.
- ZIKV spread within the CNS was facilitated by Ifnar1-deficient non-hematopoietic cells.
- ZIKV infection of astrocytes led to blood-brain barrier breakdown and CD8+ T cell influx, which limited neuronal infection but caused paralysis.
Conclusions:
- ZIKV neuropathogenesis involves blood-brain barrier disruption and T-cell-mediated damage in a susceptible mouse model.
- These findings suggest potential mechanisms for ZIKV-associated neurological complications in humans, highlighting the role of immune responses.
