Immune cells enhance Zika virus-mediated neurologic dysfunction in brain of mice with humanized immune systems

Anthony N. van den Pol, Xue Zhang, Stephen E. Maher, Alfred L.M. Bothwell

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Zika virus (ZIKV) can generate a number of neurological dysfunctions in infected humans. Here, we tested the potential of human immune cells to protect against ZIKV infection in genetically humanized MISTRG mice. FACS analysis showed robust reconstitution of the mouse spleen with human T cells. Peripheral ZIKV inoculation resulted in infection within the brains of MISTRG mice. Mice that were reconstituted with human peripheral blood mononuclear cells (PBMC) showed a more rapid lethal response to ZIKV than the control mice lacking these immune cells. Immunocytochemical analysis of T cell markers CD3, CD45, or CD8 showed strong T cell presence in the brain, together with robust infection by ZIKV particularly in the excitatory pyramidal and granule neurons of the hippocampus. Infection was also found in cortex, striatum, the dopamine neurons of the substantia nigra, and other brain loci. Infection was considerably less in other regions such as the septum and hypothalamus. These data support the perspective that, rather than exerting a protective function, T cells may underlie some ZIKV-mediated neuropathology in the brain.

Original languageEnglish (US)
Pages (from-to)389-399
Number of pages11
JournalDevelopmental Neurobiology
Volume81
Issue number4
DOIs
StatePublished - May 1 2021
Externally publishedYes

Keywords

  • Zika virus
  • humanized mice
  • lymphocytes
  • neuropathology
  • neurotropism

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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