Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir.
Intranasal infection of BALB/c mice with the WR strain of vaccinia virus leads to pneumonia, profound weight loss and death. Five days after intranasal inoculation, virus from untreated mice was recovered from 11 organs, tissues and whole blood. The highest titres [>10(8) plaque forming units (pfu)/g] were in lungs and nose/sinus tissue, with about 10(7) pfu/g in spleen and blood. Seven other organs contained 30- to > or = 50-fold lower amounts of virus. Mice infected with the related cowpox virus (for comparative purposes) had the majority of virus located in the respiratory tract. The vaccinia mouse model was used to study the efficacy of cidofovir treatments on the infection. Subcutaneous injections of 30 or 100 mg/kg/day, given on days 1 and 4 after virus challenge, reduced mortality by 60-100%. However, lung virus titres on days 2-5 were reduced no more than 10-fold by these treatments. A moderate improvement in drug efficacy occurred with daily treatments for 5 days. The efficacy of cidofovir also increased as the virus challenge dose decreased, where subcutaneous or intraperitoneal treatment routes showed similar degrees of protection. Although it has been known for many years that the WR strain of vaccinia virus can cause lethal infections by intranasal route, its application to antiviral therapy represents a new model for studying anti-orthopoxvirus agents.
Smee
D F
DF
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600, USA. dsmee@cc.usu.edu
Bailey
K W
KW
Sidwell
R W
RW
D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077404:Cidofovir; D015608:Cowpox virus / Q000302:isolation & purification; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009666:Nose / Q000821:virology; D009928:Organ Specificity; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D010256:Paranasal Sinuses / Q000821:virology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000821:virology; D013154:Spleen / Q000821:virology; D014615:Vaccinia / Q000188:drug therapy* / Q000821:virology; D014616:Vaccinia virus / Q000187:drug effects* / Q000302:isolation & purification; D019562:Viral Load; D014766:Viremia / Q000821:virology
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir