Studies on interactions of dTK-HSV mutants with neurons in vitro.

Thymidine kinase negative (dTK-) mutants of herpes simplex virus type 1 (HSV-1) multiplied well in rat brain glioma cells. A proportion (less than 1%) of glioma cells survived the infection with HSV and were designated "survivor" glioma cells. Survivor cells of dTK- mutant virus infection ceased to produce infectious virus after two passages and were highly resistant to both HSV-1 and HSV-2 but not to vesicular stomatitis virus (VSV).

Herpes simplex virus type 1 and neuronal cells--a special cell-virus interaction.

Rat brain glioma cells were semipermissive for herpes simplex virus (HSV) replication, because the growth of HSV was multiplicity-dependent in these cells. By using this property, we successfully isolated 'survivor' glioma cells following HSV infection at low multiplicity and without using any special treatment (such as UV irradiation) either of the cells or of the virus. Under the same conditions there were no survivor BHK or 3T3 cells, which suggests the uniqueness of the glioma cell-HSV interaction.

Alterations in the recognition of nucleoside analogues as substrates by the deoxythymidine kinase of a 5-methoxymethyldeoxyuridine-resistant mutant of herpes simplex virus type 1.

Inhibition constants (Kis) were used as an estimate of the ability of various nucleoside analogues to be recognized as substrates by the deoxythymidine kinases (dTKs) of a 5-methoxymethyldeoxyuridine-resistant (MMdUr) mutant of herpes simplex virus type 1 (HSV-1) and its parent wild-type (wt). It was found that the Kis for the 5-position analogues MMdU, [E]-5-(2-bromovinyl)deoxyuridine, bromodeoxyuridine and iododeoxyuridine were increased approximately three-to fivefold, suggesting that they were poorer substrates for the MMdUr dTK than for the wt dTK. With the 2' analogues arabinosylthymine and 2' fluoro 5-methylarabinosyluracil, however, the Kis were increased to a much greater extent, 80- and 240-fold, respectively.