Abstract
BackgroundMachupo virus (MACV), a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics.MethodsMice lacking signal transducer and activator of transcription 1 (STAT-1) were infected with MACV. Lethality, viral replication, metabolic changes, hematology, histopathology, and systemic cytokine expression were analyzed throughout the course of infection.ResultsWe report here that STAT-1 knockout mice succumbed to MACV infection within 7-8 days, and presented some relevant clinical and histopathological manifestations of disease. Furthermore, the model was used to validate the efficacy of ribavirin in protection against infection.ConclusionsThe STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.
Highlights
Machupo virus (MACV), a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans
The disease progression and lethality of MACV infection was assessed in signal transducer and activator of transcription 1 (STAT-1) knockout mice
Infection of STAT-1 knockout mice with ~1,000 pfu of MACV via the intraperitoneal route resulted in lethality in 6/6 mice (mean time to death (MTD) 7.3 ± 0.5) (Figure 1A)
Summary
Machupo virus (MACV), a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics. Machupo virus (MACV), a member of the Arenaviridae family, is the causative agent of Bolivian hemorrhagic fever. Histopathologic comparison of tissue from NHPs or humans that succumb to MACV infection revealed hemorrhaging and necrosis in various organs (with some differences between human and NHP findings), but none of these manifestations were thought to be severe enough to cause death [6,10]
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