Mode of antiviral action of 5-iodouracil deoxyriboside

Abstract

The effect of 5-iodouraoil deoxyriboside on the infective process in rabbit kidney cells infected with pseudorabies virus was investigated. Under the experimental conditions used, viral DNA is formed in which approximately 90% of the thymidine is replaced by 5-iodouracil deoxyriboside. Viral proteins are also synthesized by the virus-infected, drug-treated cells; however, the formation of viral particles does not occur in these cells. The lack of formation of viral particles is not due to a distortion of the DNA molecule (resulting from the presence of the drug) which prevents the enclosure of this DNA into viral coat proteins. This was concluded from the fact that viral DNA containing 5-iodouracil in both strands can be assembled into viral particles, if thymidine is supplied to the infected cells at some time during the infective process. The presence of thymidine during the early stages of infection also increases the yield of infectious virus. Evidence that these infectious viral particles contain 5-iodouracil in their DNA was provided by the fact that they are more sensitive to irradiation with 60 Co than normal, infectious viral particles. It is concluded that viral DNA containing 5-iodouracil causes the synthesis of non-functional proteins involved in virus assembly. This DNA can, however, initiate the infective process and upon replication give rise to normal thymine-containing DNA.