Related Experiment Video
Updated: Aug 8, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
The efficacy of cidofovir treatment of mice infected with ectromelia (mousepox) virus encoding interleukin-4
Samantha J Robbins1, Ronald J Jackson, Frank Fenner
1Division of Immunology and Genetics, John Curtin School of Medical Research, P.O. Box 334, Canberra, ACT 2601, Australia.
Abstract:
Improved vaccines and therapies for virulent poxvirus infection are required, particularly in the light of recent threats of bioterrorism. Cidofovir (HPMPC) is an acyclic nucleoside analog with proven efficacy against poxviruses. Here, we evaluated HPMPC in mice given a recombinant ectromelia virus (ECTV) encoding interleukin-4 (ECTV-IL-4) that is highly immune suppressive. Mousepox-sensitive BALB/c mice given HPMPC for five consecutive days after infection were protected against the lethal effects of a control ECTV recombinant, although they suffered a chronic form of mousepox disease. High doses of the drug resulted in a milder localized disease. In contrast, HPMPC failed to protect mousepox-resistant C57BL/6 mice against ECTV-IL-4, although its lethal effects were delayed by five daily doses of 20 mg/kg or a single dose of 100 mg/kg. Higher daily doses further delayed mortality, although the majority of animals eventually succumbed to infection. It appears that HPMPC inhibited ECTV-IL-4 replication without clearance, with the virus having a lethal effect when the drug was removed. Resistance of ECTV-IL-4 to HPMPC treatment may relate to the virus's ability to inhibit antiviral cell-mediated immunity. Interestingly, ECTV-IL-4-mediated immune suppression was not accompanied by a reduction in systemic IFN-gamma expression, suggestive of an alternative or highly localized suppressive mechanism.
Insights
Cidofovir (HPMPC) showed partial protection against a lethal poxvirus in mice, but the virus persisted and caused chronic disease. Resistance in some mice suggests complex immune evasion mechanisms.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Poxvirus infections pose bioterrorism threats, necessitating improved vaccines and therapies.
- Cidofovir (HPMPC), an acyclic nucleoside analog, demonstrates efficacy against poxviruses.
Purpose of the Study:
- To evaluate the efficacy of Cidofovir (HPMPC) against a highly immune-suppressive recombinant ectromelia virus (ECTV-IL-4) in mouse models.
Main Methods:
- Mice (BALB/c and C57BL/6) were infected with ECTV-IL-4 and treated with varying doses of HPMPC.
- Survival rates, disease progression, and immune responses (IFN-gamma) were monitored.
Main Results:
- HPMPC protected BALB/c mice from lethal infection but resulted in chronic disease; higher doses reduced severity.
- HPMPC delayed mortality in C57BL/6 mice but did not prevent eventual death, indicating partial efficacy.
- ECTV-IL-4 replication was inhibited by HPMPC but not cleared, with lethal effects upon drug withdrawal.
Conclusions:
- HPMPC exhibits limited efficacy against ECTV-IL-4, particularly in resistant mouse strains, suggesting viral resistance mechanisms.
- ECTV-IL-4's ability to inhibit cell-mediated immunity may contribute to HPMPC resistance.
- Immune suppression by ECTV-IL-4 occurs independently of systemic IFN-gamma reduction, pointing to localized mechanisms.
