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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\u2010mediated neuropathology in the brain.<\/jats:p>","DOI":"10.1002\/dneu.22820","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T15:45:27Z","timestamp":1617464727000},"page":"389-399","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immune cells enhance Zika virus\u2010mediated neurologic dysfunction in brain of mice with humanized immune systems"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-1660","authenticated-orcid":false,"given":"Anthony N.","family":"van den Pol","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen E.","family":"Maher","sequence":"additional","affiliation":[{"name":"Department of Immunobiology Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred L. 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