Mousepox in the C57BL/6 strain provides an improved model for evaluating anti-poxvirus therapies.

Abstract

The intranasal lethal mousepox model employing the A/Ncr mouse strain is used to evaluate anti-orthopoxvirus therapies. These infections mimic large droplet transmission and result in 100% mortality within 7-10 days with as little as 1 PFU of ectromelia virus. Unlike the A/Ncr model, humans are less susceptible to lethal respiratory infections with variola virus and monkeypox virus as demonstrated by their lower mortality rates. In this study we show that a low dose intranasal infection of C57BL/6 mice results in 60-80% mortality and better models smallpox. Comparing CMX001 (HDP-cidofovir) efficacy in the A/Ncr strain and the C57BL/6 strain revealed that delayed treatment with CMX001 is more efficacious at preventing severe disease in the C57BL/6 strain. The increased efficacy of CMX001 in C57BL/6 over A/Ncr following an intranasal infection with ectromelia appears to be mediated by a stronger Th1 cell mediated response. Following footpad infection we show that the C57BL/6 strain has earlier and more robust transcriptional activity, Th1 cytokine secretions, antigen presenting activity and IFNgamma splenic CD8+ T cell responses as compared to the A/Ncr strain. As a result of the enhanced immune response in the C57BL/6 strain, non-lethal intradermal ectromelia infections can therapeutically protect up to 3 days following a homologous, lethal intranasal infection - much like how smallpox vaccination can protect humans for up to 4 days following intranasal variola infection.

• Authors: Scott Parker, Akbar M Siddiqui, Christina Oberle, Ed Hembrador, Randall Lanier, George Painter, Alice Robertson, R Mark Buller
• Journal: Virology (Virology) Vol. 385 Issue 1 Pg. 11-21 (Mar 01 2009) ISSN: 1096-0341 [Electronic] United States
• PMID: 19100593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cytokines
• Organophosphonates
• brincidofovir
• Cytosine

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Cell Line
• Chlorocebus aethiops
• Cytokines (immunology)
• Cytosine (analogs & derivatives, therapeutic use)
• Disease Models, Animal
• Ectromelia virus (physiology)
• Ectromelia, Infectious (immunology, mortality, prevention & control)
• Female
• Mice
• Mice, Inbred C57BL
• Organophosphonates (therapeutic use)