Herpes simplex virus type 1 recombination: Role of DNA replication and viral α sequences

During the course of infection, elements of the herpes simplex virus type 1 (HSV-1) genome undergo inversion, a process that is believed to occur through the viral α sequence. To investigate the mechanism of this recombinational event, we have developed an assay that detects the deletion of DNA segments flanked by directly repeated α sequences in plasmids transiently maintained in Vero cells. With this assay, we have observed a high frequency of recombination (approximately 8%) in plasmids that undergo replication in HSV-1-infected cells. We also found a low level of recombination between α sequences in plasmids introduced into uninfected cells and in unreplicated plasmids in HSV-1-infected cells. In replicating plasmids, recombination between α sequences occurs at twice the frequency seen with directly repeated copies of a different sequence of similar size. Recombination between α sequences appears to occur at approximately the same time as replication, suggesting that the processes of replication and recombination are closely linked.