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

Details

• Alternative Title:
  PLoS Pathog
• Personal Author:
  Welch, Stephen R. ; Ritter, Jana M. ; McElroy, Anita K. ; Harmon, Jessica R. ; Coleman-McCray, JoAnn D. ; Scholte, Florine E. M. ; Kobinger, Gary P. ; Bergeron, Éric ; Zaki, Sherif R. ; Nichol, Stuart T. ; Spengler, Jessica R. ; Spiropoulou, Christina F.
• Description:
  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.
• Subjects:
  Animals Female Hemorrhagic Fever, Crimean Hemorrhagic Fever Virus, Crimean-Congo Male Mice Mice, Knockout Mononuclear Phagocyte System Receptor, Interferon Alpha-beta Viral Tropism
• Source:
  PLoS Pathog. 15(12)
• Pubmed ID:
  31790513
• Pubmed Central ID:
  PMC6984736
• Document Type:
  Journal Article
• Funding:
  P30 DK120531/DK/NIDDK NIH HHS/United States ; R01 AI109008/AI/NIAID NIH HHS/United States
• Volume:
  15
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ed1bff280352fc47ace5e312c0316b7a6cba70fda7c9ee721a175ce89f1ff2ea
• Download URL:
  https://stacks.cdc.gov/view/cdc/89858/cdc_89858_DS1.pdf
• File Type:
  [PDF - 5.49 MB ]