Herpes simplex virus DNA replication

Paul E. Boehmer, I. R. Lehman

Research output: Contribution to journalReview article

248 Scopus citations

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 languageEnglish (US)
Pages (from-to)347-384
Number of pages38
JournalAnnual Review of Biochemistry
Volume66
DOIs
StatePublished - Jul 11 1997
Externally publishedYes

Keywords

  • DNA helicase-primase
  • DNA polymerase
  • Herpesviridae
  • Origin binding protein
  • Rolling circle replication
  • Theta replication

ASJC Scopus subject areas

  • Biochemistry

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