Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge.
The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2(-5)x10(6) pfu of cowpox virus by aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals. One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%-100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl infected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunodeficiency. Treatment at the time of tail scarification with vaccinia virus did not block vaccination efficacy.
Bray
M
M
Virology Division, USAMRIID, Fort Detrick, MD 21702-5011, USA. bray@ncifcrf.gov
Martinez
M
M
Smee
D F
DF
Kefauver
D
D
Thompson
E
E
Huggins
J W
JW
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001980:Bronchi / Q000473:pathology; D000077404:Cidofovir; D015605:Cowpox / Q000188:drug therapy* / Q000517:prevention & control; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D011014:Pneumonia / Q000188:drug therapy; D011650:Pulmonary Alveoli / Q000473:pathology; D012899:Smallpox / Q000188:drug therapy / Q000517:prevention & control; D014611:Vaccination
D000336:Aerosols; D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir