Abstract
We identified some passage lineages of human herpesvirus 6 variant B (HHV-6B) strain Z29 that contain as many as 12 tandem copies of a genomic segment that corresponds almost precisely to a previously identified minimal efficient origin of lytic replication (oriLyt). Analysis of nucleotide sequences in the vicinity of the amplified segment suggests that the amplification occurred as a two-step process, with the first step being a rare sequence duplication mediated through directly repeated sequences located near the termini of the amplified segment and the second step occurring via homologous recombination through the duplicated sequence. These results demonstrate that oriLyt has been amplified in some virus stocks and indicate that (i) origin amplification confers a growth advantage on the virus in cell culture and (ii) laboratory-passaged HHV-6B genomes can accommodate additional nucleotide sequences and thus may be useful gene transfer vectors. The structures of the amplified segment and its adjacent sequences together suggest that HHV-6B or a progenitor virus acquired oriLyt by transposition from an unknown source.
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- Anders D. G., Kacica M. A., Pari G., Punturieri S. M. Boundaries and structure of human cytomegalovirus oriLyt, a complex origin for lytic-phase DNA replication. J Virol. 1992 Jun;66(6):3373–3384. doi: 10.1128/jvi.66.6.3373-3384.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Black J. B., Sanderlin K. C., Goldsmith C. S., Gary H. E., Lopez C., Pellett P. E. Growth properties of human herpesvirus-6 strain Z29. J Virol Methods. 1989 Nov;26(2):133–145. doi: 10.1016/0166-0934(89)90143-2. [DOI] [PubMed] [Google Scholar]
- Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
- Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
- Dewhurst S., Dollard S. C., Pellett P. E., Dambaugh T. R. Identification of a lytic-phase origin of DNA replication in human herpesvirus 6B strain Z29. J Virol. 1993 Dec;67(12):7680–7683. doi: 10.1128/jvi.67.12.7680-7683.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dewhurst S., Krenitsky D. M., Dykes C. Human herpesvirus 6B origin: sequence diversity, requirement for two binding sites for origin-binding protein, and enhanced replication from origin multimers. J Virol. 1994 Oct;68(10):6799–6803. doi: 10.1128/jvi.68.10.6799-6803.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inoue N., Dambaugh T. R., Rapp J. C., Pellett P. E. Alphaherpesvirus origin-binding protein homolog encoded by human herpesvirus 6B, a betaherpesvirus, binds to nucleotide sequences that are similar to ori regions of alphaherpesviruses. J Virol. 1994 Jul;68(7):4126–4136. doi: 10.1128/jvi.68.7.4126-4136.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindquester G. J., Pellett P. E. Properties of the human herpesvirus 6 strain Z29 genome: G + C content, length, and presence of variable-length directly repeated terminal sequence elements. Virology. 1991 May;182(1):102–110. doi: 10.1016/0042-6822(91)90653-s. [DOI] [PubMed] [Google Scholar]
- Lopez C., Pellett P., Stewart J., Goldsmith C., Sanderlin K., Black J., Warfield D., Feorino P. Characteristics of human herpesvirus-6. J Infect Dis. 1988 Jun;157(6):1271–1273. doi: 10.1093/infdis/157.6.1271. [DOI] [PubMed] [Google Scholar]
- Roizman B., Sears A. E. An inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol. 1987;41:543–571. doi: 10.1146/annurev.mi.41.100187.002551. [DOI] [PubMed] [Google Scholar]
- Sakagami K., Tokinaga Y., Yoshikura H., Kobayashi I. Homology-associated nonhomologous recombination in mammalian gene targeting. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8527–8531. doi: 10.1073/pnas.91.18.8527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spaete R. R., Frenkel N. The herpes simplex virus amplicon: a new eucaryotic defective-virus cloning-amplifying vector. Cell. 1982 Aug;30(1):295–304. doi: 10.1016/0092-8674(82)90035-6. [DOI] [PubMed] [Google Scholar]
- Stow N. D., Davison A. J. Identification of a varicella-zoster virus origin of DNA replication and its activation by herpes simplex virus type 1 gene products. J Gen Virol. 1986 Aug;67(Pt 8):1613–1623. doi: 10.1099/0022-1317-67-8-1613. [DOI] [PubMed] [Google Scholar]
- Thomson B. J., Efstathiou S., Honess R. W. Acquisition of the human adeno-associated virus type-2 rep gene by human herpesvirus type-6. Nature. 1991 May 2;351(6321):78–80. doi: 10.1038/351078a0. [DOI] [PubMed] [Google Scholar]
- Weller S. K., Spadaro A., Schaffer J. E., Murray A. W., Maxam A. M., Schaffer P. A. Cloning, sequencing, and functional analysis of oriL, a herpes simplex virus type 1 origin of DNA synthesis. Mol Cell Biol. 1985 May;5(5):930–942. doi: 10.1128/mcb.5.5.930. [DOI] [PMC free article] [PubMed] [Google Scholar]