A STAT-1 knockout mouse model for Machupo virus pathogenesis. Academic Article uri icon

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abstract

  • 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.Mice 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.We 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.The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.

date/time value

  • 2011

Digital Object Identifier (DOI)

  • 10.1186/1743-422X-8-300

PubMed Identifier

  • 21672221

volume

  • 8

number

keywords

  • Animals
  • Antiviral Agents
  • Arenaviridae Infections
  • Arenaviruses, New World
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Ribavirin
  • STAT1 Transcription Factor
  • Survival Analysis
  • Treatment Outcome
  • Virus Replication