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.