Identification of herpes simplex virus type 1 genes required for origin-dependent DNA synthesis

Wu, Chin-Lee; Nelson, Nancy J.; McGeoch, Duncan J.; Challberg, Mark D.

doi:10.1128/jvi.62.2.435-443.1988

Cited by 302 publications

(196 citation statements)

References 54 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…Herpesviruses encode many of the proteins necessary for viral DNA replication. Herpesvirus genes essential for viral origin-dependent DNA replication have been identi®ed, including genes for DNA polymerase, genes for an origin-binding protein and genes for a helicase/primase complex (43,44).…”

Section: Herpesvirus Proteinsmentioning

confidence: 99%

Herpesviruses in human periodontal disease

Contreras

Slots

2000

J of Periodontal Research

170

171

View full text Add to dashboard Cite

Recent studies have identified various herpesviruses in human periodontal disease. Epstein-Barr virus type 1 (EBV-1) infects periodontal B-lymphocytes and human cytomegalovirus (HCMV) infects periodontal monocytes/ macrophages and T-lymphocytes. EBV-1, HCMV and other herpesviruses are present more frequently in periodontitis lesions and acute necrotizing ulcerative gingivitis-lesions than in gingivitis or periodontally healthy sites. Reactivation of HCMV in periodontitis lesions tends to be associated with progressing periodontal disease. Herpesvirus-associated periodontitis lesions harbor elevated levels of periodontopathic bacteria, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteriodes forsythus, Prevotella intermedia, Prevotella nigrescens and Treponema denticola. It may be that active periodontal herpesvirus infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. Alteration between latent and active herpesvirus infection in the periodontium might lead to transient local immunosuppression and explain in part the episodic progressive nature of human periodontitis. Tissue tropism of herpesvirus infections might help explain the localized pattern of tissue destruction in periodontitis. Absence of herpesvirus infection or viral reactivation might explain why some individuals carry periodontopathic bacteria while still maintaining periodontal health. Further studies are warranted to delineate whether the proposed herpesvirus-periodontopathic bacteria model might account for some of the pathogenic features of human periodontal disease.

show abstract

Section: Herpesvirus Proteinsmentioning

confidence: 99%

Herpesviruses in human periodontal disease

Contreras

Slots

2000

J of Periodontal Research

170

171

View full text Add to dashboard Cite

show abstract

“…The HSV-1 genome encodes seven proteins that are required for origin-dependent DNA replication. They consist of a DNA polymerase and its accessory protein, a heterotrimeric helicase-primase, a single-strand (ss) DNA-binding protein and an originbinding protein, termed UL9 (Elias et al, 1986;McGeoch et al, 1988;Wu et al, 1988;Challberg and Kelly, 1989;Crute et al, 1989). Key to understanding the early events in HSV-1 replication as in other systems is learning how UL9 protein interacts with the HSV-1 origins of replication and how it may alter the structure of the DNA at the origin.…”

Section: Introductionmentioning

confidence: 99%

The herpes simplex virus type 1 origin-binding protein carries out origin specific DNA unwinding and forms stem-loop structures.

et al. 1996

View full text Add to dashboard Cite

The UL9 protein of herpes simplex virus type 1 (HSV‐1) binds specifically to the HSV‐1 oriS and oriL origins of replication, and is a DNA helicase and DNA‐dependent NTPase. In this study electron microscopy was used to investigate the binding of UL9 protein to DNA fragments containing oriS. In the absence of ATP, UL9 protein was observed to bind specifically to oriS as a dimer or pair of dimers, which bent the DNA by 35 degrees +/− 15 degrees and 86 degrees +/− 38 degrees respectively, and the DNA was deduced to make a straight line path through the protein complex. In the presence of 4 mM ATP, binding at oriS was enhanced 2‐fold, DNA loops or stem‐loops were extruded from the UL9 protein complex at oriS, and the DNA in them frequently appeared highly condensed into a tight rod. The stem‐loops contained from a few hundred to over one thousand base pairs of DNA and in most, oriS was located at their apex, although in some, oriS was at a border. The DNA in the stem‐loops could be stabilized by photocrosslinking, and when Escherichia coli SSB protein was added to the incubations, it bound the stem‐loops strongly. Thus the DNA strands in the stem‐loops exist in a partially paired, partially single‐stranded state presumably making them available for ICP8 binding in vivo. These observations provide direct evidence for an origin specific unwinding by the HSV‐1 UL9 protein and for the formation of a relatively stable four‐stranded DNA in this process.

show abstract

“…The gene encoding 65KDBP maps in the HindIII L fragment and corresponds to UL42 (26). Sev_ral pieces of evidence indicate that 65KDBP is involved in DNA replication: (i) UL42 is one of only seven HSV-1 genes required for the replication of plasmids containing an HSV origin of replication (44); (ii) a temperature-sensitive mutant with a lesion which maps to coordinates occupied by UL42 does not synthesize viral DNA at the nonpermissive temperature (20); and (iii) 65KDBP is closely associated with the viral DNA polymerase (Pol), suggesting that it is a component of replication complexes (9,42).…”

mentioning

confidence: 99%

Kinetics of expression of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1

Goodrich

Rixon

Parris

1989

J Virol

View full text Add to dashboard Cite

The 65-kilodalton DNA-binding protein (65KDBp) of herpes simplex virus type 1, encoded by gene UL42, is required for herpes simplex virus origin-dependent DNA replication (C. A. Wu, N. J. Nelson, D. J. McGeoch, and M. D. Challberg, J. Virol. 62:435-443, 1988). We found by indirect immunofluorescence with monoclonal antibody to 65KDBP that the protein was first detectable at 3 h postinfection. It localized first to the inner periphery of the nucleus, but accumulated in large globular compartments within the nucleus by 6 h postinfection in a pattern similar to that displayed by the major DNA-binding protein ICP8. Immune electron microscopy revealed that 65KDBP was associated with the marginated heterochromatin at the early times, but migrated further into the nucleus at late times when the only discernible areas devoid of 65KDBP were the nucleoli and heterochromatin. The 65KDBP gene is a member of the 0i kinetic class as determined by the ability of the mRNA to be expressed at significant levels even in the absence of viral DNA synthesis. Furthermore, in the presence or absence of the DNA polymerase inhibitor phosphonoacetic acid, the patterns of accumulation of protein as well as mRNA were virtually indistinguishable from those displayed by the model 0 genes encoding ICP8 and thymidine kinase. Nuclear run-on experiments demonstrated that maximum rates of

show abstract

Identification of herpes simplex virus type 1 genes required for origin-dependent DNA synthesis

Cited by 302 publications

References 54 publications

Herpesviruses in human periodontal disease

Herpesviruses in human periodontal disease

The herpes simplex virus type 1 origin-binding protein carries out origin specific DNA unwinding and forms stem-loop structures.

Kinetics of expression of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1

Contact Info

Product

Resources

About