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Chapter 14 : Herpes Simplex Virus DNA Replication and Genome Maturation

Author: Sandra K. Weller1
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Affiliations: 1: Department of Microbiology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030
Content Type: Monograph
Publication Year: 1995

Category: Viruses and Viral Pathogenesis; Microbial Genetics and Molecular Biology

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Abstract:

This chapter gives an overview on the replication and maturation of the herpes simplex virus type 1 (HSV-1) genome, drawing parallels with phage systems. It provides an overview of what is known about HSV DNA replication and recombination under the sections Formation of circular DNA Intermediates, Formation of greater-than-unit-length replication intermediates, Resolution of branched recombination intermediates, and Cleavage of concatemers into unit-length virion DNA and packaging of unit-length virion DNA into capsids. The chapter concentrates on the helicase-primase (UL5, UL8, and UL52) and the origin-binding protein (UL9). The study of transdominant mutations has proven to be a powerful tool for characterizing specific regions of multifunctional proteins. Several lines of evidence indicate that overexpression of the wild-type UL9 protein can be inhibitory to viral replication. First, in trans-dominance assays, plasmids that express wild-type UL9 are somewhat inhibitory to plaque formation by wild-type virus. Second, complementing cell lines that contain high copy numbers of a UL9 expression plasmid do not efficiently support wild-type HSV-1 infection are reported. The third line of evidence comes from experiments in which the HSV replication proteins are expressed in insect cells from recombinant baculoviruses. Several lines of evidence suggest that viral genome maturation involves site-specific cleavage of viral DNA concatemers. Genetic analysis has provided important insights not only into the identification of viral proteins required in DNA replication and genome maturation but also into their roles in these complex processes.

Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14

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Herpes Simplex Virus DNA Replication and Genome Maturation
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Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14
/content/10.1128/9781555818302.chap14.fig14-1
Figure 1

Model of T4 DNA replication and recombination. Recombination-dependent late DNA replication of T4 is depicted here. The topmost sketch represents a linear molecule that has replicated at an origin of replication. At the end of the molecule, a free 3' end that cannot be replicated is generated. (A) The 3' end of the parental DNA strand invades a homologous segment of another molecule. (B) Leading-strand synthesis can be primed from the 3' end of the invading DNA strand. Lagging-strand synthesis would require the activity of primase. (C) This process can be repeated with a new 3' end invading another molecule. Heavy solid lines represent parental DNA molecules. Thin solid lines represent DNA synthesized following initiation at an origin of replication. Thin dashed lines represent DNA synthesized following recombination events. This figure was based on the model of T4 DNA replication described by Mosig ( ).

10.1128/9781555818302/fig14-1_thmb.gif
10.1128/9781555818302/fig14-1.gif
Image of Figure 1
Figure 1

Model of T4 DNA replication and recombination. Recombination-dependent late DNA replication of T4 is depicted here. The topmost sketch represents a linear molecule that has replicated at an origin of replication. At the end of the molecule, a free 3' end that cannot be replicated is generated. (A) The 3' end of the parental DNA strand invades a homologous segment of another molecule. (B) Leading-strand synthesis can be primed from the 3' end of the invading DNA strand. Lagging-strand synthesis would require the activity of primase. (C) This process can be repeated with a new 3' end invading another molecule. Heavy solid lines represent parental DNA molecules. Thin solid lines represent DNA synthesized following initiation at an origin of replication. Thin dashed lines represent DNA synthesized following recombination events. This figure was based on the model of T4 DNA replication described by Mosig ( ).

Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14
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Figure 2

Locations of HSV origins and genes encoding DNA synthetic functions. The sequence arrangement of the HSV-1 genome is shown on the top line. Locations of the origins of DNA replication are depicted on the second line. On the third line are map locations of genes that encode functions involved in DNA synthesis. Genes and origins are not drawn to scale.

10.1128/9781555818302/fig14-2_thmb.gif
10.1128/9781555818302/fig14-2.gif
Image of Figure 2
Figure 2

Locations of HSV origins and genes encoding DNA synthetic functions. The sequence arrangement of the HSV-1 genome is shown on the top line. Locations of the origins of DNA replication are depicted on the second line. On the third line are map locations of genes that encode functions involved in DNA synthesis. Genes and origins are not drawn to scale.

Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14
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Figure 3

Conserved helicase motifs and motif mutations in The gene is shown with six black boxes depicting each of the motifs shared within a superfamily of helicases. Below are shown the mutations introduced into conserved residues within each motif ( ). aas, amino acids.

10.1128/9781555818302/fig14-3_thmb.gif
10.1128/9781555818302/fig14-3.gif
Image of Figure 3
Figure 3

Conserved helicase motifs and motif mutations in The gene is shown with six black boxes depicting each of the motifs shared within a superfamily of helicases. Below are shown the mutations introduced into conserved residues within each motif ( ). aas, amino acids.

Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14
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Figure 4

Conserved helicase motifs and motif mutations in The gene is shown with six black boxes depicting each of the motifs shared within a superfamily of helicases. The putative leucine zipper within the N-terminal portion of is represented by a hatched box overlapping motif II. The DNA-binding C-terminal domain is depicted by a stippled box. Below are shown the mutations introduced into conserved residues within each motif ( ). aas, amino acids.

10.1128/9781555818302/fig14-4_thmb.gif
10.1128/9781555818302/fig14-4.gif
Image of Figure 4
Figure 4

Conserved helicase motifs and motif mutations in The gene is shown with six black boxes depicting each of the motifs shared within a superfamily of helicases. The putative leucine zipper within the N-terminal portion of is represented by a hatched box overlapping motif II. The DNA-binding C-terminal domain is depicted by a stippled box. Below are shown the mutations introduced into conserved residues within each motif ( ). aas, amino acids.

Citation: Weller S. 1995. Herpes Simplex Virus DNA Replication and Genome Maturation, p 189-213. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch14
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