Herpes simplex virus type 1 recombinants without the oriL sequence replicate DNA with increased fidelity

Herpes simplex virus type 1 (HSV-1) contains three DNA replication origins (ori) of two types. The oriL is located in the center of the unique long sequences, whereas two copies of oriS, which are structurally different from oriL, are within the reiterated sequences flanking the unique short sequences. Recombinant viruses were constructed from ts+7, which contains a deletion of oriL sequences, to have either the beta-galactosidase gene or the supF amplicon integrated into the thymidine kinase locus. Rescue recombinants also were constructed from the supF-containing recombinant to restore the deleted oriL to the wild type sequences. These recombinants were subjected to mutagenesis assays. Results demonstrated that ts+7 viruses with the deletion in oriL sequences replicated both target genes with higher fidelity compared to those derived from the parental strain KOS. Possible mechanisms leading to the high fidelity of DNA replication mediated by viruses without intact oriL sequences are discussed.