In vitro effect of acyclovir and other antiherpetic compounds on the replication of channel catfish virus.

The antiviral effect of acyclovir (ACV; 9-(2-hydroxyethoxymethyl)guanine) on the replication of channel catfish virus (CCV), a poikilothermic herpesvirus, in brown bullhead cells (BB) was studied in vitro. Acyclovir at concentrations of 2 microM and 10 microM produced a 95 to 99% reduction in plaque numbers, respectively. At 10 microM ACV did not affect the growth of uninfected BB cells which could even be subcultured for four passages in the presence of the inhibitor. To be effective ACV had to be added early in the infectious cycle and was progressively less effective when added at later times after infection. Similar to homeothermic herpesviruses, the inhibition could be reversed with the addition of excess thymidine. The effects of three other antiviral agents, adenine-beta-D-arabinofuranoside (ara-A), phosphonoacetic acid (PAA), and phosphonoformic acid (PFA) on CCV replication were evaluated either individually or in combination with ACV. Although the other agents were found to be less effective in inhibiting CCV replication than ACV, none of the agents interacted synergistically with ACV. The results indicated that interactions with ACV with ara-A, PFA and PAA were primarily additive. Mutants of CCV resistant to ACV were obtained and were found to be somewhat more resistant to PFA than was the stock CCV.