Study on the apparent resistant strains of herpes simplex virus type 1 against 9-beta-D-arabinofuranosyladenine.

The appearance of drug resistant strains of herpes simplex virus type 1 (HSV-1) against 9-beta-D-arabinofuranosyladenine (araA), in comparison with 5-iodo-2'-deoxyuridine (IUdR) and 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine, ACG), has been investigated in green monkey kidney cell cultures (Vero) and human embryo lung cell cultures (HEL). Growth curves of HSV-1 in Vero cells and HEL cells in the presence or absence of 20 micrograms/ml of araA showed that not only the viruses produced by these cells in the presence of araA but also the viruses produced in the absence of araA were resistant to the same concentration of araA. However, both viruses were unable to grow in the presence of a combination of 20 micrograms/ml of araA and 3 micrograms/ml of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) which is an inhibitor of adenosine deaminase. On the other hand, the viruses produced only in the presence of IUdR or ACG were resistant to each drug. All virus clones obtained from five serial clonings in the presence of araA alone or araA and EHNA in combination were not resistant to araA. These results show that the strain of HSV-1 resistant to araA is an apparently resistant strain, and a truly resistant strain to araA may not be established as easily as the truly resistant strains to IUdR and ACG.