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

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/ß 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.

Evaluation of renal involvement in children with Crimean-Congo hemorrhagic fever.

The aim of the present study was to evaluate renal involvement in children with Crimean-Congo hemorrhagic fever (CCHF). Forty-four children infected with CCHF virus and 30 controls were enrolled in the study. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine protein levels were measured in the patient and control groups. Clinical and laboratory findings of the patient and control groups were compared. uNGAL levels were higher in the patient group than that in the control group (P < 0.001). Of the 44 patients, 26 (59.1%) were proteinuric. uNGAL levels in proteinuric patients were higher than those in non-proteinuric patients (P = 0.035). There was a positive correlation between uNGAL and urine protein levels in the patient group. (R = 0.614, P < 0.001). Due to renal involvement, increased proteinuria and increased uNGAL levels were observed in children with CCHF. In these children, measuring urine total protein and uNGAL levels can be useful to monitor renal involvement due to CCHF.