title: A STAT-1 knockout mouse model for Machupo virus pathogenesis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Bradfute
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Stuthman
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shurtleff
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001117:Arenaviridae Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D006477:Arenaviruses, New World / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012254:Ribavirin / Q000627:therapeutic use; D050794:STAT1 Transcription Factor / Q000172:deficiency*; D016019:Survival Analysis; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D012254:Ribavirin