Inhibition of sindbis virus replication by ribavirin: Influence of cultural conditions and of the host cell phenotype

Abstract

Several factors which influence the ability of ribavirin to inhibit the replication of Sindbis virus in baby hamster kidney (BHK) cells are described; these include the cell passage level, the presence of serum in the medium and cell density. Inhibition of viral replication was much more effective with low passage cells than with high passage cells. However, with high passage cells antiviral activity was enhanced 1) when subconfluent cultures were infected, rather than confluent cultures, and 2) when infected cultures were maintained in the presence of serum rather than without serum. Under all conditions, a good correlation was found between the inhibition of virus replication by ribavirin and its ability to reduce cellular GTP levels. Using Chinese hamster ovary cell mutants we found that ribavirin inhibited Sindbis virus replication in cells lacking hypoxanthine phosphoribosyltransferase (HPRT −) but not in HPRT + cells. This result and the demonstration that Aedes albopictus cells (in which ribavirin is very effective) are unable to incorporate hypoxanthine suggest that certain salvage enzymes involved in purine metabolism can interfere with the antiviral activity of ribavirin.