Studies of the effects of 5-iodo-2′-deoxyuridine on the formation of adenovirus type 2 virions and the synthesis of virus-induced polypeptides

Abstract

The antiviral activity of 5-iodo-2′-deoxyuridine (IdUrd) on human adenovirus type 2 (Ad2) was examined. The loss of infectivity, resulting from the presence of IdUrd in the medium, was greater than either the decrease in the number of viral particles produced or the increase in yield of incomplete particles. A “new” species of viral particle with a lower buoyant density than other known incomplete particles was identified at the higher concentrations of IdUrd tested. In the presence of 10 μg/ml of IdUrd, the specific infectivity of the complete particles was 0.04 per cent that of control. No difference in mobilities or molar ratios of the structural proteins derived from these completed virions was detected by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The buoyant density of the viral DNA derived from virions grown in the presence of IdUrd was higher in CsCl than that of control viral DNA, although both samples of DNA sedimented at the same rate in neutral and alkaline sucrose density gradients. The loss of infectivity after replication in media supplemented with IdUrd is associated not only with a reduced yield in total particles formed and an enhanced formation of incomplete particles, but also with the production of noninfectious substituted complete virions. The biosynthesis of virus-induced polypeptides in the presence or absence of IdUrd was analyzed. No apparent inhibition of early virus-induced proteins was detected even at very high doses of the analog. On the other hand, the synthesis of late viral proteins was inhibited markedly; the degree of inhibition was related directly to the concentration of IdUrd in the medium. Our studies suggest that IdUrd exerts its antiviral effect after incorporation into viral progeny DNA. The loss in the biological integrity of such substituted DNA molecules is not accompanied by fragmentation. The molecular basis for the inhibitory effect of IdUrd on the replication of Ad2 remains to be elucidated.