A Variant of Herpes Simplex Virus Type 2 Strain HG52 with a 1.5 kb Deletion in RL between 0 to 0.02 and 0.81 to 0.83 Map Units Is Non-neurovirulent for Mice

Abstract

SUMMARYThe virulence of a deletion variant of herpes simplex virus type 2 (HSV-2) strain HG52 has been determined by intracranial inoculation of 3-week-old BALB/c mice.The variant JH2604 has a 1.5 kb deletion within each copy of the long repeat region (RL) of the genome between 0 to 0.02 and 0-81 to 0.83 map units. JH2604 is avirulent for mice compared to the parental wild-type virus, and fails to replicate in mouse brain in vivo. Correction of the deletion by marker rescue resulted in the isolation of recombinants which gave LD50 values comparable to those of individual plaque stocks of the parental HG52. Introduction of the deletion into wild-type virus resulted in recombinants which on intracranial inoculation of mice were avirulent. The results imply that sequences within the 3 kb terminal portion of RE are required for virulence of HSV-2 strain HG52.

High efficiency gene transfer to the central nervous system of rodents and primates using herpes virus vectors lacking functional ICP27 and ICP34.5

“…following intracerebral inoculation into mice. 8,14 Despite this however, mutants lacking functional ICP34.5 can replicate in vitro in dividing cells and can also establish latency in vivo. 15,16 They thus represent an excellent candidate for gene therapy vectors with no requirement for growth in a complimenting cell line and hence no possibility of reversion to a neurovirulent phenotype.…”

ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro

“…Mutants which fail to express ICP34.5 are incapable of causing encephalitis and destroying central nervous system neurons following intracerebral inoculation of mice (Taha et al, 1989a, b;MacLean et al, 1991). Lack of ICP34.5 expression does not impair virus replication in laboratory tissue culture cells [BHK-21 (C13)] or in mouse peripheral skin tissue in vivo.…”

Construction and characterization of herpes simplex type 1 viruses without introns in immediate early gene 1

“…Since sequences upstream of the IE-1 region are involved in pathogenicity (Taha et al, 1989;Thompson et al, 1989) and a transcript containing these sequences continues throughout the IE-1 region (Chou and Roizman, 1986), it seemed possible that information within the IE-1 introns might also be involved in pathogenicity. However, preliminary data from intracranial inoculation experiments in mice indicate that the pathogenicity of the 110C viruses is not impaired (L. Robertson & S. M. Brown, personal communication).…”

“…IE-1 is overlapped in the same sense by a transcript originating in the 'a' sequence (Chou & Roizman, 1986), the coding potential of which was controversial (McGeoch et al, 1988) until published sequences were extensively revised (Chou & Roizman, 1990). Sequences immediately 5' to IE-1, within this transcribed region, are important for the pathogenicity of both HSV-1 and -2 (Taha et al, 1989;Thompson et al, 1989). In the opposite orientation, IE-1 is overlapped by the latency-associated transcripts (LATs), which are the only viral transcripts expressed at high levels in latently infected neurons (although their role in latency remains unclear).…”