Unusual regulation of expression of the herpes simplex virus DNA polymerase gene

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 determine how ICP27 promotes amplification of viral DNA, we examined the synthesis, accumulation, and stability of the essential viral replication proteins and steady-state levels of the replication gene transcripts throughout the course of ICP27 mutant virus infections. These studies reveal that in the absence of ICP27, expression of the UL5, UL8, UL52, UL9, UL42, and UL30 genes is significantly reduced at the level of mRNA accumulation. In contrast to that of these ␤ genes, ICP8 expression is unaltered in mutant virus-infected cells, indicating that ICP27 selectively stimulates only a subset of herpes simplex virus ␤ genes. Analysis of multiple ICP27 mutant viruses indicates a quantitative correlation between the ability of these mutants to replicate viral DNA and the level of replication proteins produced by each mutant. Therefore, we conclude that the primary defect responsible for restricted viral DNA synthesis in cells infected with ICP27 mutants is insufficient expression of most of the essential replication genes. Of further interest, this analysis also provides new information about the structure of the UL52 gene transcripts.

Section: Discussionsupporting

confidence: 90%

Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes

Uprichard

Knipe

1996

“…5). The UL9 transcript is therefore an early gene product whose synthesis is reduced in the presence of PAA, as in the case of the UL30 gene, which encodes viral DNA polymerase (74).…”

Section: Fig 3 S1 Analysis Of the Ul10 Transcript (A) (Top) Locatimentioning

confidence: 99%

Transcriptional analysis of the region of the herpes simplex virus type 1 genome containing the UL8, UL9, and UL10 genes and identification of a novel delayed-early gene product, OBPC

Baradaran

Dabrowski

Schaffer

1994

“…Consequently, E genes are not homogeneous with respect to activation by ICP4. Additionally, activation of some E genes, like UL9 and UL30, may be further complicated by their unusual sensitivity to the status of DNA replication (4,74). There is also the possibility that some E genes are differentially regulated in neurons; for example, the UL9 promoter has been reported to contain a cyclic AMP response element and to be differentially induced in PC12 cells (14).…”

Section: Discussionmentioning

confidence: 99%

The Polyserine Tract of Herpes Simplex Virus ICP4 Is Required for Normal Viral Gene Expression and Growth in Murine Trigeminal Ganglia

Bates

DeLuca

1998

ICP4 of herpes simplex virus (HSV) is essential for productive infection due to its central role in the regulation of HSV transcription. This study identified a region of ICP4 that is not required for viral growth in culture or at the periphery of experimentally inoculated mice but is critical for productive growth in the trigeminal ganglia. This region of ICP4 encompasses amino acids 184 to 198 and contains 13 nearly contiguous serine residues that are highly conserved among the alphaherpesviruses. A mutant in which this region is deleted (ΔSER) was able to grow on the corneas of mice and be transported back to the trigeminal ganglia. ΔSER did not grow in the trigeminal ganglia but did express low levels of several immediate-early (ICP4 and ICP27) and early (thymidine kinase [tk] and UL42) genes. It expressed very low levels of the late gC gene and did not appear to replicate DNA. This pattern of gene expression was similar to that observed for a tk mutant,dlsptk. Both ΔSER and dlsptk expressed higher levels of the latency-associated transcript (LAT) per genome earlier in infected ganglia than did the wild-type virus, KOS. However, infected ganglia from all three viruses accumulated the same level of LAT per genome at 30 days postinfection (during latency). The data suggest that the polyserine tract of ICP4 provides an activity that is required for lytic infection in ganglia to progress to viral DNA synthesis and full lytic gene expression. In the absence of this activity, higher levels of LAT per genome accumulate earlier in infection than with wild-type virus.