Sl. Uprichard et Dm. Knipe, HERPES-SIMPLEX ICP27 MUTANT VIRUSES EXHIBIT REDUCED EXPRESSION OF SPECIFIC DNA-REPLICATION GENES, Journal of virology, 70(3), 1996, pp. 1969-1980
Herpes simplex virus type 1 mutants with certain lesions in the ICP27
gene show a 5- to 10-fold reduction in viral DNA synthesis. To determi
ne how ICP27 promotes amplification of viral DNA, we examined the synt
hesis, accumulation, and stability of the essential viral replication
proteins and steady-state levels of the replication gene transcripts t
hroughout the course of ICP27 mutant virus infections. These studies r
eveal that in the absence of ICP27, expression of the UL5, UL8, UL52,
UL9, UL42, and UL30 genes is significantly reduced at the level of mRN
A accumulation. In contrast to that of these beta genes, ICP8 expressi
on is unaltered in mutant virus-infected cells, indicating that ICP27
selectively stimulates only a subset of herpes simplex virus beta gene
s. Analysis of multiple ICP27 mutant viruses indicates a quantitative
correlation between the ability of these mutants to replicate viral DN
A and the level of replication proteins produced by each mutant. There
fore, we conclude that the primary defect responsible for restricted v
iral DNA synthesis in cells infected with ICP27 mutants is insufficien
t expression of most of the essential replication genes. Of further in
terest, this analysis also provides new information about the structur
e of the UL52 gene transcripts.