Oropouche virus causes acute hepatitis in mice controlled by type I interferons

Area of Science:

• Virology
• Hepatology
• Immunology

Background:

• Oropouche virus (OROV) is a South American arbovirus causing significant public health concern.
• A recent OROV outbreak shows a dramatic increase in cases and severe outcomes like encephalitis and death.
• The liver's role in OROV pathogenesis, from mild hepatitis to severe coagulopathy, is underrecognized.

Purpose of the Study:

• To investigate Oropouche virus pathogenesis and its impact on the liver.
• To develop and characterize mouse models for studying OROV-induced hepatic disease.
• To compare the pathogenicity of contemporary and historical OROV strains.

Main Methods:

• Establishment of two mouse models: one for lethal OROV hepatic disease and one for self-resolving acute hepatitis.
• Induction of OROV hepatic necrosis and assessment of lethality, particularly with Type I interferon receptor antagonism.
• Comparative analysis of a contemporary OROV isolate versus a historic prototypical strain in a lethal mouse model.

Main Results:

• OROV causes focal hepatic necrosis in mice, progressing to massive necrosis and death when Type I interferon signaling is blocked.
• A contemporary OROV isolate demonstrated lower pathogenicity in mice compared to a historic strain.
• The developed models mimic both lethal and self-resolving OROV hepatitis seen in human cases.

Conclusions:

• The study provides valuable mouse models for understanding Oropouche virus pathogenesis and liver involvement.
• These models are crucial for preclinical evaluation of potential vaccines and therapeutics against OROV.
• Findings highlight the need for further research into OROV-induced liver disease and strain-specific virulence.