Virulence of and establishment of latency by genetically engineered deletion mutants of herpes simplex virus 1.

We report the results of studies on the biologic properties of seven deletion mutants of herpes simplex virus 1 (HSV-1). The genes deleted from six of these mutants map in the S component of HSV-1 DNA and include those specifying the alpha protein 47, the glycoproteins G and E, the viral protein kinase, and two proteins whose functions are not yet known (open reading frames US2 and US11). The seventh virus [HSV-1(F) delta 305] contained a 700-bp deletion in the thymidine kinase gene. The results of intracerebral inoculation of Balb/c mice indicated that all but one of the deletion mutants in the S component were significantly attenuated. The PFU/LD50 ratios for these mutants ranged from 10(4)- to 10(5)-fold higher than that of the wild-type, HSV-1(F). The PFU/LD50 for mutant R7032, from which the glycoprotein E gene had been deleted, was less than 100-fold higher than that of the parent virus. All of the mutants, with one exception, were able to establish latency in mice; the exception, HSV-1(F) delta 305, was able to establish latency in rabbits.