Related Experiment Video
Updated: May 12, 2026
Measurement of γHV68 Infection in Mice
Published on: November 22, 2011
Lymphocytic choriomeningitis virus infection in FVB mouse produces hemorrhagic disease
Frederick J Schnell1, Sarah Sundholm, Stacy Crumley
1Sarepta Therapeutics, Corvallis, Oregon, United States of America.
Abstract:
The viral family Arenaviridae includes a number of viruses that can cause hemorrhagic fever in humans. Arenavirus infection often involves multiple organs and can lead to capillary instability, impaired hemostasis, and death. Preclinical testing for development of antiviral or therapeutics is in part hampered due to a lack of an immunologically well-defined rodent model that exhibits similar acute hemorrhagic illness or sequelae compared to the human disease. We have identified the FVB mouse strain, which succumbs to a hemorrhagic fever-like illness when infected with lymphocytic choriomeningitis virus (LCMV). FVB mice infected with LCMV demonstrate high mortality associated with thrombocytopenia, hepatocellular and splenic necrosis, and cutaneous hemorrhage. Investigation of inflammatory mediators revealed increased IFN-γ, IL-6 and IL-17, along with increased chemokine production, at early times after LCMV infection, which suggests that a viral-induced host immune response is the cause of the pathology. Depletion of T cells at time of infection prevented mortality in all treated animals. Antisense-targeted reduction of IL-17 cytokine responsiveness provided significant protection from hemorrhagic pathology. F1 mice derived from FVB×C57BL/6 mating exhibit disease signs and mortality concomitant with the FVB challenged mice, extending this model to more widely available immunological tools. This report offers a novel animal model for arenavirus research and pre-clinical therapeutic testing.
Insights
A new mouse model using FVB mice infected with lymphocytic choriomeningitis virus (LCMV) effectively mimics human hemorrhagic fever. This model aids in developing antiviral therapies for arenavirus infections.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Arenaviridae viruses cause hemorrhagic fever, often fatal in humans.
- Current preclinical models lack immunological definition for arenavirus research.
- Developing effective therapeutics is hindered by inadequate animal models.
Purpose of the Study:
- To identify and characterize a novel rodent model for arenavirus-induced hemorrhagic fever.
- To investigate the immunological mechanisms underlying arenavirus hemorrhagic pathology.
- To validate the utility of this model for preclinical antiviral therapeutic testing.
Main Methods:
- Infection of FVB mice with lymphocytic choriomeningitis virus (LCMV).
- Assessment of mortality, clinical signs, and histopathological changes.
- Analysis of inflammatory mediators (cytokines, chemokines) and immune cell populations.
- Evaluation of therapeutic interventions including T cell depletion and IL-17 targeted antisense therapy.
Main Results:
- FVB mice infected with LCMV exhibited high mortality, thrombocytopenia, organ necrosis, and hemorrhage.
- Elevated levels of IFN-γ, IL-6, and IL-17 were observed early post-infection.
- T cell depletion completely prevented mortality.
- Targeting IL-17 responsiveness significantly reduced hemorrhagic pathology.
- A crossbreed (F1) mouse model demonstrated similar disease progression.
Conclusions:
- FVB mice provide a viable model for studying arenavirus hemorrhagic fever.
- The pathology is driven by the host's immune response, particularly involving T cells and IL-17.
- This model is suitable for preclinical evaluation of antiviral drugs and immunotherapies.
