Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- mice

Autoři: Stephen R. Welch aff001;  Jana M. Ritter aff002;  Anita K. McElroy aff001;  Jessica R. Harmon aff001;  JoAnn D. Coleman-McCray aff001;  Florine E. M. Scholte aff001;  Gary P. Kobinger aff004;  Éric Bergeron aff001;  Sherif R. Zaki aff002;  Stuart T. Nichol aff001;  Jessica R. Spengler aff001;  Christina F. Spiropoulou aff001
Působiště autorů: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America aff001;  Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America aff002;  Division of Pediatric Infectious Disease, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of Pittsburgh, Center for Vaccine Research Pittsburgh, Pennsylvania, United States of America aff003;  Department of Microbiology, Immunology and Infectious Diseases, Université Laval, Quebec City, Quebec, Canada aff004
Vyšlo v časopise: Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- mice. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008183
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008183


Crimean-Congo hemorrhagic fever virus (CCHFV, order Bunyavirales, family Nairoviridae, genus Orthonairovirus) is the tick-borne etiological agent of Crimean-Congo hemorrhagic fever (CCHF) in humans. Animals are generally susceptible to CCHFV infection but refractory to disease. Small animal models are limited to interferon-deficient mice, that develop acute fatal disease following infection. Here, using a ZsGreen1- (ZsG) expressing reporter virus (CCHFV/ZsG), we examine tissue tropism and dissemination of virus in interferon-α/β receptor knock-out (Ifnar-/-) mice. We demonstrate that CCHFV/ZsG retains in vivo pathogenicity comparable to wild-type virus. Interestingly, despite high levels of viral RNA in all organs assessed, 2 distribution patterns of infection were observed by both fluorescence and immunohistochemistry (IHC), corresponding to the permissiveness of organ tissues. To further investigate viral dissemination and to temporally define cellular targets of CCHFV in vivo, mice were serially euthanized at different stages of disease. Flow cytometry was used to characterize CCHFV-associated alterations in hematopoietic cell populations and to classify infected cells in the blood, lymph node, spleen, and liver. ZsG signal indicated that mononuclear phagocytic cells in the lymphatic tissues were early targets of infection; in late-stage infection, overall, the highest levels of signal were detected in the liver, and ZsG was found in both antigen-presenting and lymphocyte cell populations.

Klíčová slova:

Cytokines – Flow cytometry – Immunostaining – Liver – Lymph nodes – Macrophages – Mouse models – Spleen


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