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A STAT-1 knockout mouse model for Machupo virus pathogenesis

Steven B Bradfute1, Kelly S Stuthman, Amy C Shurtleff

  • 1United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.

Virology Journal
|June 16, 2011
PubMed
Abstract

Insights

A new STAT-1 knockout mouse model effectively mimics lethal Machupo virus infection, showing disease manifestations and validating ribavirin as a potential treatment for Bolivian hemorrhagic fever.

Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • Machupo virus (MACV) causes Bolivian hemorrhagic fever with high lethality.
  • Understanding MACV pathogenesis and developing treatments are hindered by a lack of suitable animal models.

Purpose of the Study:

  • To develop and characterize a small animal model for lethal MACV infection.
  • To utilize the model for preliminary drug efficacy testing.

Main Methods:

  • Infection of signal transducer and activator of transcription 1 (STAT-1) knockout mice with MACV.
  • Analysis of lethality, viral replication, metabolic and hematologic changes, histopathology, and cytokine expression.

Main Results:

  • STAT-1 knockout mice exhibited lethality within 7-8 days post-infection.
  • The model displayed relevant clinical and histopathological features of MACV disease.
  • Ribavirin efficacy was validated in this model.

Conclusions:

  • The STAT-1 knockout mouse is a valuable model for studying lethal MACV infection.
  • This model facilitates drug testing and immunological investigations for Bolivian hemorrhagic fever.

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