Pathological Manifestations of Intranasally RVFV MP12 Infected IFNAR and NSG Mouse Models

Introduction Rift Valley fever (RVF) is a zoonotic disease caused by RVF Virus (RVFV). Most infected humans develop self-limiting febrile illness, while in rare cases RVFV infections result in severe symptoms, such as encephalitis with late neurological disorders. For this study, the role of type I interferon (IFN-I) for the RVF progression in the CNS is investigated using IFNAR^-/--mice. In addition, NOD scid gamma (NSG) mice were also used to examine the possibility of an immune-mediated RVF encephalitis (RVFE).

Material and Methods C57BL/6 (WT), IFNAR^-/-, and NSG mice were intranasally infected with 10³ PFU of RVFV MP12. The mice were clinically evaluated twice daily for 21 days. Mice were then sacrificed; organ samples were histologically examined and analyzed by immunohistochemistry, immunofluorescence and qPCR.

Results WT mice did not develop histological lesions and RVFV RNA was not detected in brain and liver, except for one WT mouse that developed meningoencephalitis at 14 dpi, which was associated with high viral load. All IFNAR^-/- mice died 4-5 dpi and developed hepatocellular necrosis with high viral load but no CNS lesions. Interestingly, a low amount of virus was found in the brain of these mice. NSG mice displayed mild CNS lesions with high virus load in the brain. Immunofluorescence demonstrated neuronal tropism of RVFV.

Conclusions The results showed that the IFN-I system is essential for protection against RVFV infection and prevention of liver injury. CNS lesions in NSG mice point towards virus induced and not immune-mediated RVFE. Fatal hepatitis in IFNAR^-/- mice at 4-5 dpi prevented the development of encephalitis at later time points. Thus, in the next step of the study, cell-type specific IFNAR^-/- mice will be used to elucidate the role of neurons and astrocytes in the prevention of RVFE.

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Artikel online veröffentlicht:
13. Juni 2025