Abstract
The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virus type- 1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for origin-specific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5'-3' DNA helicase and primase activities, and an origin-binding protein with 3'-5' DNA helicase activity, HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for vital replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase α-primase, DNA ligase I, and topoisomerase II, are probably also required. Following circularization of the linear vital genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 347-384 |
| Number of pages | 38 |
| Journal | Annual Review of Biochemistry |
| Volume | 66 |
| DOIs | |
| State | Published - 1997 |
| Externally published | Yes |
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Keywords
- DNA helicase-primase
- DNA polymerase
- Herpesviridae
- Origin binding protein
- Rolling circle replication
- Theta replication
ASJC Scopus subject areas
- Biochemistry
Cite this
Herpes simplex virus DNA replication. / Boehmer, Paul E; Lehman, I. R.
In: Annual Review of Biochemistry, Vol. 66, 1997, p. 347-384.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Herpes simplex virus DNA replication
AU - Boehmer, Paul E
AU - Lehman, I. R.
PY - 1997
Y1 - 1997
N2 - The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virus type- 1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for origin-specific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5'-3' DNA helicase and primase activities, and an origin-binding protein with 3'-5' DNA helicase activity, HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for vital replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase α-primase, DNA ligase I, and topoisomerase II, are probably also required. Following circularization of the linear vital genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
AB - The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virus type- 1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for origin-specific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5'-3' DNA helicase and primase activities, and an origin-binding protein with 3'-5' DNA helicase activity, HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for vital replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase α-primase, DNA ligase I, and topoisomerase II, are probably also required. Following circularization of the linear vital genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
KW - DNA helicase-primase
KW - DNA polymerase
KW - Herpesviridae
KW - Origin binding protein
KW - Rolling circle replication
KW - Theta replication
UR - http://www.scopus.com/inward/record.url?scp=0031008223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031008223&partnerID=8YFLogxK
U2 - 10.1146/annurev.biochem.66.1.347
DO - 10.1146/annurev.biochem.66.1.347
M3 - Article
C2 - 9242911
AN - SCOPUS:0031008223
VL - 66
SP - 347
EP - 384
JO - Annual Review of Biochemistry
JF - Annual Review of Biochemistry
SN - 0066-4154
ER -