Schematic representation of the derivation of R7020 (aka NV1020). This virus was constructed for the purpose of creating a vaccine for HSV-1 and HSV-2 that would be administered by intramuscular injection of living virus.138 HSV-1(F) was initially deleted for thymidine kinase (UL23) and UL24. The internal set of the inverted repeats, containing α0, α4, γ134.5, ORF O, and ORF P, was replaced with a novel construct that contained UL23 fused to the α4 promoter-regulatory region and 3′ to a series of HSV-2 genes (US2, HSV protein kinase, US5, glycoproteins G, D, and I, as well as a portion of E). The terminal inverted repeat remained intact. Thus, this chimeric virus, containing both HSV-1 and HSV-2 sequences, has been extensively tested in both rodent and primate species for safety (LD50 = 2.7 × 106 PFU versus 3.8 × 102 PFU for HSV-1(F)) and genetic stability.138,139