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Characterization of a STAT-1 Knockout Mouse Model for Machupo Virus Infection and Pathogenesis.

Stephanie R Monticelli^1,2, Ana I Kuehne², Russell R Bakken²

¹Viral Immunology Branch, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.

|July 30, 2025

Summary

This summary is machine-generated.

Researchers developed a lethal mouse model for Machupo virus (MACV), the cause of Bolivian hemorrhagic fever. This model mimics human disease progression, showing a two-phase illness with neurological effects and mortality.

Keywords:

Machupo virus STAT1 arenavirus arenavirus mouse models

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Area of Science:

Virology
Immunology
Infectious Diseases

Background:

Machupo virus (MACV) causes Bolivian hemorrhagic fever with high human mortality.
STAT-1 deficient mice typically succumb to MACV, but partial lethality was observed.

Purpose of the Study:

To investigate the temporal progression of MACV infection in STAT-1 deficient mice.
To develop a lethal small rodent model of MACV infection that recapitulates human disease.

Main Methods:

Serial sampling and pathological evaluation of STAT-1 deficient mice after MACV challenge.
Development of a mouse-adapted MACV (maMACV) through tissue adaptation in the brain.

Main Results:

MACV infection in STAT-1 deficient mice followed a two-phase course: initial systemic infection, followed by lethal neuroinvasion.
Mouse adaptation of MACV (maMACV) resulted in a fully lethal model with accelerated neurodissemination and pathology.

Conclusions:

A lethal small rodent model for MACV infection was established.
This model effectively recapitulates key pathological and clinical features of human Bolivian hemorrhagic fever.