The herpes simplex virus type 1 UL6 protein is essential for cleavage and packaging but not for genomic inversion

Abstract

The HSV-1 genome is composed of two unique regions (U(L) and U(S)) flanked by inverted repeats. During the course of DNA replication the two unique regions U(L) and U(S) invert relative to one another. In this report we present evidence that cleavage is not necessary for genomic inversion to occur. We isolated and characterized a UL6::lacZ insertion mutant (hr74) that produces wild-type levels of replicating viral DNA but fails to cleave and package DNA. We demonstrate that this virus is still able to undergo genomic inversion. Furthermore we confirm that replicating DNA from cells infected with wild-type virus contains specific U(L) termini but not U(S) termini, whereas cells infected with the mutant hr74 do not contain either U(S) or U(L) termini. This demonstrates that the specific U(L) ends found in replicating DNA are the result of the cleavage/packaging process.