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

• Type of Material: Article
• Authors: Jessica R. Spengler, Centers for Disease Control and Prevention; M Kelly Keating, Centers for Disease Control and Prevention; Anita McElroy, Emory University; Marko Zivcec, Centers for Disease Control and Prevention; JoAnn D Coleman-McCray, Centers for Disease Control and Prevention; Jessica R. Harmon, Centers for Disease Control and Prevention; Brigid C. Bollweg, Centers for Disease Control and Prevention; Cynthia S Goldsmith, Centers for Disease Control and Prevention; Eric Bergeron, Centers for Disease Control and Prevention; James G. Keck, The Jackson Laboratory; Sherif R. Zaki, Centers for Disease Control and Prevention; Stuart Nichol, Emory University; Christina F. Spiropoulou, Centers for Disease Control and Prevention
• Language: English
• Date: 2017-12-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Final Published Version
• Copyright Statement: Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jix215
• Title of Journal or Parent Work: Journal of Infectious Diseases
• ISSN: 0022-1899
• Volume: 216
• Issue: 11
• Start Page: 1386
• End Page: 1397
• Grant/Funding Information: This work was partially supported by an appointment to the Research Participation Program at the CDC administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC, by the National Institutes of Health (loan repayment award to J. R. S.), and by a CDC foundation project funded by the National Institute of Allergy and Infectious Diseases (grant R01AI109008 to E. B.).
• Keywords: VIRUS-INFECTION; Microbiology; glial cell; TRANSMISSION; Immunology; NEURONS; NSG-SGM3 humanized mice; LIVESTOCK; RESPONSES; JUNIN VIRUS; neuropathology; Life Sciences & Biomedicine; Crimean-Congo hemorrhagic fever; meningitis; INTERFERON; PATHOGENESIS; LETHAL; Science & Technology; Infectious Diseases; CCHF
• Research Categories: Biology, Cell; Health Sciences, Pathology; Health Sciences, Public Health

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.