Accession Number:

ADA544463

Title:

A STAT-1 Knockout Mouse Model for Machupo Virus Pathogenesis

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

2011-06-14

Pagination or Media Count:

24.0

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.

Subject Categories:

  • Medicine and Medical Research
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE