DNA sequence and RNA transcription through a site of recombination in a non-neurovirulent herpes simplex virus intertypic recombinant

Abstract

RE6 is a herpes simplex type-1 (HSV-1) X herpes simplex type-2 (HSV-2) intertypic recombinant that cannot replicate in the adult mouse nervous system. In the accompanying report, we have shown that HSV-1 sequences between 0.698 and 0.721 map units can restore a partial neurovirulent phenotype to RE6. In this report, we have used comparative DNA sequence analysis of RE6, 17syn+ (HSV-1) and HG52 (HSV-2) to demonstrate that this region contains a site of recombination between HSV-1 and HSV-2 sequences in RE6. High resolution transcription analysis has demonstrated that three readily detected transcripts are present in this region of the genome. In addition, the 5' end of a low abundance 5 kb transcript was also located in the right-hand portion of this region. All the transcripts encoded by HSV-1 and HSV-2 in this region of the genome are expressed by the RE6 recombinant. This and our sequence data suggest that the lack of neurovirulence in RE6 is not due to a simple loss in the expression of a transcript or to a defect in a protein encoded by a gene at the site of recombination.