1887

Abstract

Dideoxynucleotide sequence analysis of a spontaneously isolated deletion variant (1714) of Glasgow strain 17 of herpes simplex virus type 1 (HSV-1) demonstrates that the deletion is 759 bp in length and is located within each copy of the HI fragment (0 to 0.02 and 0.81 to 0.83 map units) of the long repeat region of the genome. The deletion removes one complete copy of the 18 bp DR element of the ‘a’ sequence and terminates 1105 bp upstream of the 5′ end of immediate early (IE) gene 1. The variant grows to high titre, is not temperature-sensitive and is not host cell type-restricted studies demonstrate that 1714 is totally avirulent for BALB/c mice following intracerebral inoculation, with an LD of 7 × 10 p.f.u./mouse compared to < 10 p.f.u./mouse for the parental wild-type strain 17. growth kinetics show that the non-neurovirulent phenotype is due to an inability to replicate in mouse brain. Because 1714 was in a genomic background in which the four I sites had been removed and because the phenotype was thymidine kinase-negative, the 759 bp deletion was introduced into an otherwise totally wild-type background. The resulting variant (1716) is nonneurovirulent for mice, with an LD of 7 × 10 p.f.u./mouse. The deletion does not prevent the virus from establishing a latent infection or reactivating from it The results demonstrate that sequences between IE-1 and the ‘a’ sequence produce neurovirulence in Glasgow strain 17 and, in conjunction with the nonneurovirulence of the HSV-2 HG52 variant JH2604, identify a common function conserved in HSV-1 and -2.

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1991-03-01
2021-10-21
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