Isomerization of herpes simplex virus 1 genome: identification of the cis-acting and recombination sites within the domain of the a sequence.

Previous studies have shown that the a sequence located at the termini and at the junction between the L and S components is the site-specific, cis-acting sequence mediating the inversions of herpes simplex virus 1 DNA. We constructed mutated a sequences, inserted them into the thymidine kinase gene, and recombined them into the L component of the viral genome. Deletion of Uc or Ub domains of the a sequence did not affect inversions, whereas the deletion of direct repeat #4 (DR4) drastically reduced their frequency. Deletion of both direct repeat #2 (DR2) and DR4 abolished inversions. Recombinational events leading to inversions appear to occur through DR2, and possibly DR4. These results complement previous studies showing that most of one DR1 sequence can also be dispensed with and are consistent with the hypothesis that DR4 and possibly DR2 are the cis-acting sites for the inversions mediated by the a sequence.