Herpes simplex virus 1 recombinants with noninverting genomes frozen in different isomeric arrangements are capable of independent replication.

Herpes simplex virus 1 genome consists of two covalently linked components, L and S, that invert relative to each other to yield four equimolar isomeric populations designated P (prototype), Is (inversion of S component), Il (inversion of L component), and Ils (inversion of L and S components) differing in the orientation of the two components. Previous studies have yielded recombinant genomes frozen in the P isomeric arrangement, reinforcing suggestions that the four isomers may not be functionally equivalent. We report the isolation of recombinants produced by insertional mutagenesis with alpha TK mini-Mu that are frozen in Is and Ils arrangements. Thus, all isomeric forms of herpes simplex virus DNA appear to be capable of independent replication and must be considered as functionally equivalent.