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10 - Alphaherpesvirus DNA replication
- from Part II - Basic virology and viral gene effects on host cell functions: alphaherpesviruses
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- By John Hay, Witebsky Center for Microbial Pathogenesis and Immunology, SUNY at Buffalo School of Medicine, NY, USA, William T. Ruyechan, Witebsky Center for Microbial Pathogenesis and Immunology, SUNY at Buffalo School of Medicine, NY, USA
- Edited by Ann Arvin, Stanford University, California, Gabriella Campadelli-Fiume, Università degli Studi, Bologna, Italy, Edward Mocarski, Emory University, Atlanta, Patrick S. Moore, University of Pittsburgh, Bernard Roizman, University of Chicago, Richard Whitley, University of Alabama, Birmingham, Koichi Yamanishi, University of Osaka, Japan
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- Book:
- Human Herpesviruses
- Published online:
- 24 December 2009
- Print publication:
- 16 August 2007, pp 138-143
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Summary
DNA replication in alphaherpesviruses has been the subject of study in bursts over the years. Interest in the subject depends not just on simple curiosity about this central feature of the viral growth cycle, but also because DNA replication is a potentially useful target for antiviral therapy, as has already been shown with agents such as acyclovir. The viral contributions to the mechanism of genome replication are quite well understood but we still are unable to duplicate the in vivo situation in an in vitro assay. Much of the recent interesting work involves the host cell's contribution to the process, and this seems likely to remain a focus for the future.
Structure of the genome
There are over 30 alphaherpesviruses that infect a wide range of host species. Their genomes fall into two general categories, either herpes simplex (HSV) – like or varicella zoster (VZV) – like, with four or two, respectively, isomeric forms (Fig. 10.1). There is a wide range of G + C content (32%–75%), with a bias towards higher (>50%) numbers. There is also size heterogeneity (125–180 kbp) which, although quantitatively less than the nucleotide composition variation, may be much more significant for the lifestyle of the virus. All alphaherpesvirus genomes contain four general structural components: unique long and short (UL, US) sequences that encode single-copy genes and inverted repeat regions that bound the unique regions; these may contain diploid genes and sequences required for cleavage and packaging of viral DNA (Fig. 10.1).
3 - DNA replication
- from Part II - Molecular Biology and Pathogenesis
- Edited by Ann M. Arvin, Stanford University School of Medicine, California, Anne A. Gershon, Columbia University, New York
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- Book:
- Varicella-Zoster Virus
- Published online:
- 02 March 2010
- Print publication:
- 23 November 2000, pp 51-73
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Summary
Structure and physical properties of VZV DNA
The varicella-zoster virus (VZV) genome is a linear double-stranded DNA molecule consisting of approximately 125000 base pairs with an average G + C content of 46%. Computer analysis of the sequence predicted the presence of approximately 70 open reading frames (ORFs). The genome is similar in overall structure to other alphaherpesvirus DNAs and its significant colinearity with the herpes simplex virus type 1 (HSV-1) sequence facilitated assignment of the ORFs (Davison & Scott, 1986). The VZV genome consists of two covalently linked segments, L and S, which are in turn composed of unique sequences UL and US. These unique regions are bounded by inverted repeat sequences IRL/TRL and IRS/TRS, respectively (Figure 3.1). In the genome of the Dumas strain, which was completely sequenced by Davison & Scott (1986), the UL region consists of 104 836bp flanked by 88.5 bp inverted repeats and the US region consists of 5232bp flanked by 7319.5 bp inverted repeats. These data are consistent with earlier estimates of the size of the genome derived from electron microscopic measurements, restriction enzyme analysis, and the overall G + C content estimated by bouyant density (Ludwig et al., 1972; Dumas et al., 1980, 1981; Straus et al., 1981; Davison & Scott, 1983).
Analysis of restriction enzyme digests of DNA derived from purified virions of numerous strains indicated that unlike the herpes simplex genome, which has a distinctive strain-dependent restriction fragment fingerprint, only a few “geographic” restriction fragment polymorphisms present or absent in VZV DNA genomes isolated in Asia or western Europe and the US were observed.