Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells As Primary Targets of Neurological Infection

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2017 May 9

PMID 28482001

Citations 42

Authors

Jessica R Spengler

M Kelly Keating

Anita K McElroy

Marko Zivcec

JoAnn D Coleman-McCray

Jessica R Harmon

Brigid C Bollweg

Cynthia S Goldsmith

Eric Bergeron

James G Keck

Sherif R Zaki

Stuart T Nichol

Christina F Spiropoulou

Affiliations

Soon will be listed here.

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF.

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