Inversion of the two segments of the herpes simplex virus genome in intertypic recombinants.

We have analysed by restriction site mapping the structures of the termini and L-S joint in several HSV-1/HSV-2 intertypic recombinants, including Bx1(28-1), the virion DNA of which has a marked overabundance of one orientation of the L segment, and subclones of Bx1(28-1). All recombinants with both orientations of L present in equal amounts contain TRL and IRL regions derived at least in part from the same parent (HSV-1 or HSV-2) as a result of previously undetected crossovers in these regions. Recombinants with a predominance of one orientation of L have TRL and IRL regions derived from different parents. Homology between a sequences alone at the L terminus and L-S joint is sufficient for normal inversion of L. Analysis of another recombinant, RE4, which fails to invert normally in both L and S, suggests that normal inversion of S is dependent upon the presence of TRS and IRS regions derived at least in part from the same parent. We conclude that segment inversion specifically depends upon the a sequence, that the process of DNA replication and maturation does not necessarily produce molecules with identical a sequences, and that direct ligation of termini may occur during DNA replication.