Mousepox in the C57BL/6 strain provides an improved model for evaluating anti-poxvirus therapies
| Autor: | Alice Robertson, Randall Lanier, Scott Parker, George R. Painter, Akbar M. Siddiqui, Ed Hembrador, Christina Oberle, R. Mark L. Buller |
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| Jazyk: | angličtina |
| Předmět: |
C57BL/6
Ectromelia virus Ectromelia animal diseases viruses Organophosphonates Antiviral Agents Article Cell Line Cytosine Mice Immune system Antigen Virology Chlorocebus aethiops medicine Animals Ectromelia Infectious Antiviral biology virus diseases biology.organism_classification medicine.disease Bioterrorism Mice Inbred C57BL Disease Models Animal Immunology Monkeypox virus Cytokines Oral drug Female Variola virus CD8 Cidofovir Smallpox |
| Zdroj: | Virology. (1):11-21 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2008.11.015 |
| Popis: | 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 IFNγ 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. |
| Databáze: | OpenAIRE |
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