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Development and characterization of a guinea pig model for Marburg virus

Gary Wong1,2,3,4, Wen-Guang Cao1,4, Shi-Hua He1

  • 1Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.

Zoological Research
|March 8, 2018
PubMed

Insights

Researchers developed a Marburg virus variant (MARV/Ang-GA) lethal in guinea pigs. This new model aids in screening Marburg virus therapeutics and understanding viral adaptation for improved disease control.

Area of Science:

  • Virology
  • Infectious Diseases
  • Animal Models

Background:

  • The Angolan strain of Marburg virus (MARV/Ang) is highly lethal in humans (up to 90% fatality) but does not cause symptoms in immunocompetent rodents.
  • Previous development of a mouse-lethal MARV/Ang variant (MARV/Ang-MA) necessitates an intermediate animal model for preclinical studies before non-human primate testing.

Purpose of the Study:

  • To develop and characterize a Marburg virus variant that causes lethal disease in guinea pigs, serving as an intermediate animal model.
  • To investigate the pathological features and genetic mutations of the MARV/Ang variant in guinea pigs.

Main Methods:

  • Serial passage of the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs.
  • Characterization of clinical signs, viremia, organ distribution, and mortality in infected guinea pigs.
  • Identification and comparison of mutations in the MARV/Ang-GA variant against known rodent-adapted MARV/Ang strains.

Main Results:

  • A MARV/Ang variant (MARV/Ang-GA) emerged, causing 100% lethality in guinea pigs.
  • MARV/Ang-GA infection led to typical filovirus symptoms: lymphocytopenia, thrombocytopenia, high viremia, and systemic organ spread.
  • The median lethal dose (LD50) of MARV/Ang-GA was determined to be 1.1×10-1 TCID50, with death occurring 7-9 days post-infection.

Conclusions:

  • MARV/Ang-GA is a lethal variant in guinea pigs, establishing a valuable intermediate animal model for Marburg virus research.
  • This model can facilitate the screening of prophylactic and therapeutic candidates and aid in understanding Marburg virus host adaptation.
Keywords:
Animal modelGuinea pigHost adaptationMarburg virusPathogenesis

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