Ribavirin mitigates wart growth in rabbits at early stages of infection with cottontail rabbit papillomavirus.
The challenge to develop antiviral agents effective against DNA viruses such as human papillomavirus (HPV) has been dependent on finding an animal model which mimics the human forms of the disease. We have used an existing model system for the purpose of measuring the effect of antiviral drugs on the inhibition of growth of these lesions. This was based upon domestic rabbits which efficiently grow cutaneous papillomas (warts) when infected with cottontail rabbit papillomavirus (CRPV). One agent which had shown significant success in achieving these goals was ribavirin. Ribavirin was administered intradermally shortly prior to infection at multiple sites with CRPV. Following daily injections of this drug for eight weeks, we have shown a dose-dependent response which had markedly reduced the number of warts, the time of first appearance of warts and reduced the tumor mass as compared to placebo-treated control animals. At the highest dose of ribavirin tested, 30 mg/kg/day, compared to controls, the average reduction in the number of warts was 52%, the average time of first appearance of warts was 49% longer, and the average mass of the warts was reduced by 98%. No detectable antibodies to CRPV were observed in any of the animals. The only side effects which were observed was focal alopecia, and a decrease in body growth upon prolonged treatment, both of which were completely reversible. Pharmacokinetic studies established the metabolism of ribavirin over a 24-h period of time. Ribavirin administered beginning 12 or 30 days post-infection, while not reducing the number of warts, slightly retarded the growth of warts as determined by date of first appearance of warts and mass of warts.
Ostrow
R S
RS
Institute of Human Genetics, University of Minnesota Medical School, Minneapolis.
Forslund
K M
KM
McGlennen
R C
RC
Shaw
D P
DP
Schlievert
P M
PM
Ussery
M A
MA
Huggins
J W
JW
Faras
A J
AJ
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D007271:Injections, Intradermal; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D011817:Rabbits; D012044:Regression Analysis; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014860:Warts / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
D000914:Antibodies, Viral; D004279:DNA, Viral; D012254:Ribavirin