The use of intertypic recombinants for analysis of gene organization in herpes simplex virus.

Analysis of the DNA sequence arrangement and polypeptides specified by 28 HSV-1 x HSV-2 recombinants show the following: (i) Recombinants with heterogeneous L and S components or with heterogenous inverted repeats are viable. (ii) HSV-1 and HSV-2 genes appear to be functionally equivalent and with few exceptions co-linearly arranged. Co-linear DNA maps have been established. (iii) At most two arrangements of HSV DNA are capable of replication. This is consistant with current studies suggesting that sequence arrangements are the consequence of obligatory post-synthesis repair. (iv) alpha Polypeptides map at the termini of the L and S components of HSV DNA. Although alpha ICP 27 maps entirely within the reiterated region of the L component, the template for alpha ICP 4 may lie only in part within the reiterated sequences of the S component. Of note is the finding that cells infected with a recombinant that contains both HSV-1 and HSV-2 DNA sequences in the S component, produced alpha ICP 4 of both HSV-1 and HSV-2. (v) Templates specifying beta and gamma polypeptides may in the L component and appear to be randomly distributed. (vi) The genes specifying thymidine kinase, resistance to phosphonoacetic acid and syncytial plaque morphology mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis to map the gene(s) specifying this inhibition in the L component.