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Hemorrhagic Fever Disease in STAT-1 Knockout Mice Infected with Lujo Virus
Dylan M Johnson1,2,3, Sharon Jan2, Ethan Dunn2
1Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
Abstract:
Lujo virus (LUJV) is an arenavirus that causes Lujo Hemorrhagic Fever (LHF), a viral hemorrhagic fever that emerged in a 2007 outbreak in Zambia and South Africa with an 80% case fatality rate and evidence of human-to-human nosocomial transmission. There are no approved medical countermeasures for LHF, although several screens have identified lead antiviral compounds. The lack of accessible animal models limits the development of lead compounds and characterization of broadly protective anti-arenavirus compounds such as ribavirin for the treatment of LHF. Here, we present preliminary data characterizing the partially lethal disease caused by LUVJ in STAT-1 deficient mice. Several key hematological, clinical chemistry, and histologic findings common to LHF disease are recapitulated in this model. This work suggests that further characterization of LUJV infection in STAT-1 deficient mice may allow development of a model that would be instrumental in the development of medical countermeasures for LHF.
Insights
Lujo virus (LUJV) causes severe Lujo Hemorrhagic Fever (LHF). STAT-1 deficient mice partially recapitulate LHF, offering a potential model for developing medical countermeasures against this deadly arenavirus.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Lujo virus (LUJV) causes Lujo Hemorrhagic Fever (LHF), a severe illness with high fatality and human-to-human transmission.
- No approved medical countermeasures exist for LHF, hindering effective treatment strategies.
Purpose of the Study:
- To characterize the disease caused by LUJV in STAT-1 deficient mice.
- To evaluate the potential of this model for developing antiviral therapies and broadly protective compounds for LHF.
Main Methods:
- Infection of STAT-1 deficient mice with LUJV.
- Monitoring of hematological, clinical chemistry, and histological parameters.
- Assessment of disease severity and recapitulation of LHF clinical findings.
Main Results:
- STAT-1 deficient mice developed a partially lethal disease upon LUJV infection.
- Key hematological, clinical chemistry, and histological findings consistent with LHF were observed in the mouse model.
- The model demonstrated potential for studying LHF pathogenesis.
Conclusions:
- STAT-1 deficient mice offer a promising preclinical model for Lujo Hemorrhagic Fever.
- This model can aid in the development and testing of medical countermeasures for LHF and other arenaviral infections.
