Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection.
OBJECTIVE
To test the life-sparing and therapeutic effect of a parenterally administered virus-specific antiviral phosphorodiamidate morpholino oligomer (PMO) for treating kittens during outbreaks of severe viral disease.


METHODS
112 kittens of various sex and age in 4 trials involving 3 outbreaks of naturally developing caliciviral disease.


METHODS
Each trial provided an opportunity to investigate the disease. A calicivirus isolated from the liver of a cat that died with hemorrhage and hepatitis was sequenced, and a PMO that had sequence specificity complementary to a 5' region was synthesized. In vitro efficacy of the PMO was tested against the isolate, followed by 3 trials in outbreaks of severe caliciviral disease. The PMO was administered starting on day 1 of disease onset (0.7 to 5.0 mg/kg, SC, q 24 h) and continuing for up to 7 days. Survival time, clinical recovery, and caliciviral shedding were compared by use of various antiviral dosages. In a fourth trial involving nonfatal disease, a control treatment was administered for comparison.


RESULTS
In vitro blockage of caliciviral replication by the PMO was dose dependent. In trials 1 to 3 in which survival was the endpoint, 47 of 59 cats receiving PMO survived but only 3 of 31 survived without PMO treatment. Antiviral treatment reduced viral shedding and hastened clinical recovery, as measured by weight gains and clinical condition.


CONCLUSIONS
These data provided evidence that virus-specific PMOs were effective in treating kittens with severe Vesivirus disease and suggested a broader application for other viruses and species, including humans.
Smith
Alvin W
AW
Laboratory for Calicivirus Studies, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Iversen
Patrick L
PL
O'Hanley
Peter D
PD
Skilling
Douglas E
DE
Christensen
Janet R
JR
Weaver
Sherry S
SS
Longley
Kimberli
K
Stone
Michael A
MA
Poet
Steve E
SE
Matson
David O
DO
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D017250:Caliciviridae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000662:veterinary*; D017927:Calicivirus, Feline; D002371:Cat Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D002415:Cats; D004196:Disease Outbreaks / Q000662:veterinary*; D005260:Female; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D060172:Morpholinos
D000998:Antiviral Agents; D009025:Morpholines; D060172:Morpholinos