Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Mar;71(3):2390–2399. doi: 10.1128/jvi.71.3.2390-2399.1997

Formation of herpes simplex virus type 1 replication compartments by transfection: requirements and localization to nuclear domain 10.

C J Lukonis 1, S K Weller 1
PMCID: PMC191349  PMID: 9032376

Abstract

During infection, the seven essential herpes simplex virus type 1 (HSV-1) replication proteins are found in globular nuclear structures called replication compartments. Replication compartments form adjacent to ND10, nuclear matrix-bound domains which are present in most cell types but whose function is unknown (G. G. Maul, I. M. Ishov, and R. D. Everett, Virology 217:67-75, 1996). We now demonstrate that replication compartments can be formed by cotransfecting Vero cells with constructs expressing the seven essential viral replication proteins and a plasmid containing an HSV-1 origin of DNA replication. Like replication compartments in infected cells, replication compartments formed by cotransfection contain all of the essential viral replication proteins, are sites of DNA synthesis, and are found adjacent to ND10. However, neither the viral origin-binding protein nor a plasmid containing an HSV-1 origin of DNA replication is individually required for the formation of transfection replication compartments, although the presence of each increases the efficiency of replication compartment formation. Further, we provide evidence that UL29 independently localizes adjacent to ND10 and so may play a role in directing replication compartments to these preexisting nuclear structures.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ascoli C. A., Maul G. G. Identification of a novel nuclear domain. J Cell Biol. 1991 Mar;112(5):785–795. doi: 10.1083/jcb.112.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berezney R., Mortillaro M. J., Ma H., Wei X., Samarabandu J. The nuclear matrix: a structural milieu for genomic function. Int Rev Cytol. 1995;162A:1–65. doi: 10.1016/s0074-7696(08)61228-0. [DOI] [PubMed] [Google Scholar]
  3. Boehmer P. E., Craigie M. C., Stow N. D., Lehman I. R. Association of origin binding protein and single strand DNA-binding protein, ICP8, during herpes simplex virus type 1 DNA replication in vivo. J Biol Chem. 1994 Nov 18;269(46):29329–29334. [PubMed] [Google Scholar]
  4. Boehmer P. E., Lehman I. R. Physical interaction between the herpes simplex virus 1 origin-binding protein and single-stranded DNA-binding protein ICP8. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8444–8448. doi: 10.1073/pnas.90.18.8444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carvalho T., Seeler J. S., Ohman K., Jordan P., Pettersson U., Akusjärvi G., Carmo-Fonseca M., Dejean A. Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies. J Cell Biol. 1995 Oct;131(1):45–56. doi: 10.1083/jcb.131.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Challberg M. D. A method for identifying the viral genes required for herpesvirus DNA replication. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9094–9098. doi: 10.1073/pnas.83.23.9094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curtin K. D., Knipe D. M. Altered properties of the herpes simplex virus ICP8 DNA-binding protein in cells infected with ICP27 mutant viruses. Virology. 1993 Sep;196(1):1–14. doi: 10.1006/viro.1993.1449. [DOI] [PubMed] [Google Scholar]
  8. Deppert W., Schirmbeck R. The nuclear matrix and virus function. Int Rev Cytol. 1995;162A:485–537. doi: 10.1016/s0074-7696(08)61237-1. [DOI] [PubMed] [Google Scholar]
  9. Dorsky D. I., Crumpacker C. S. Expression of herpes simplex virus type 1 DNA polymerase gene by in vitro translation and effects of gene deletions on activity. J Virol. 1988 Sep;62(9):3224–3232. doi: 10.1128/jvi.62.9.3224-3232.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dyck J. A., Maul G. G., Miller W. H., Jr, Chen J. D., Kakizuka A., Evans R. M. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell. 1994 Jan 28;76(2):333–343. doi: 10.1016/0092-8674(94)90340-9. [DOI] [PubMed] [Google Scholar]
  11. Ebert S. N., Subramanian D., Shtrom S. S., Chung I. K., Parris D. S., Muller M. T. Association between the p170 form of human topoisomerase II and progeny viral DNA in cells infected with herpes simplex virus type 1. J Virol. 1994 Feb;68(2):1010–1020. doi: 10.1128/jvi.68.2.1010-1020.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Everett R. D., Maul G. G. HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J. 1994 Nov 1;13(21):5062–5069. doi: 10.1002/j.1460-2075.1994.tb06835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gao M., Knipe D. M. Distal protein sequences can affect the function of a nuclear localization signal. Mol Cell Biol. 1992 Mar;12(3):1330–1339. doi: 10.1128/mcb.12.3.1330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goddard A. D., Borrow J., Freemont P. S., Solomon E. Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science. 1991 Nov 29;254(5036):1371–1374. doi: 10.1126/science.1720570. [DOI] [PubMed] [Google Scholar]
  15. Goldstein D. J., Toyama R., Dhar R., Schlegel R. The BPV-1 E5 oncoprotein expressed in Schizosaccharomyces pombe exhibits normal biochemical properties and binds to the endogenous 16-kDa component of the vacuolar proton-ATPase. Virology. 1992 Oct;190(2):889–893. doi: 10.1016/0042-6822(92)90932-f. [DOI] [PubMed] [Google Scholar]
  16. Goodrich L. D., Schaffer P. A., Dorsky D. I., Crumpacker C. S., Parris D. S. Localization of the herpes simplex virus type 1 65-kilodalton DNA-binding protein and DNA polymerase in the presence and absence of viral DNA synthesis. J Virol. 1990 Dec;64(12):5738–5749. doi: 10.1128/jvi.64.12.5738-5749.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Greenfield I., Nickerson J., Penman S., Stanley M. Human papillomavirus 16 E7 protein is associated with the nuclear matrix. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11217–11221. doi: 10.1073/pnas.88.24.11217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grussenmeyer T., Scheidtmann K. H., Hutchinson M. A., Eckhart W., Walter G. Complexes of polyoma virus medium T antigen and cellular proteins. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7952–7954. doi: 10.1073/pnas.82.23.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Guldner H. H., Szostecki C., Grötzinger T., Will H. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. J Immunol. 1992 Dec 15;149(12):4067–4073. [PubMed] [Google Scholar]
  20. Hardwicke M. A., Schaffer P. A. Cloning and characterization of herpes simplex virus type 1 oriL: comparison of replication and protein-DNA complex formation by oriL and oriS. J Virol. 1995 Mar;69(3):1377–1388. doi: 10.1128/jvi.69.3.1377-1388.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Heilbronn R., zur Hausen H. A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome. J Virol. 1989 Sep;63(9):3683–3692. doi: 10.1128/jvi.63.9.3683-3692.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ishov A. M., Maul G. G. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol. 1996 Aug;134(4):815–826. doi: 10.1083/jcb.134.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kakizuka A., Miller W. H., Jr, Umesono K., Warrell R. P., Jr, Frankel S. R., Murty V. V., Dmitrovsky E., Evans R. M. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. doi: 10.1016/0092-8674(91)90112-c. [DOI] [PubMed] [Google Scholar]
  24. Kastner P., Perez A., Lutz Y., Rochette-Egly C., Gaub M. P., Durand B., Lanotte M., Berger R., Chambon P. Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J. 1992 Feb;11(2):629–642. doi: 10.1002/j.1460-2075.1992.tb05095.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Klinedinst D. K., Challberg M. D. Helicase-primase complex of herpes simplex virus type 1: a mutation in the UL52 subunit abolishes primase activity. J Virol. 1994 Jun;68(6):3693–3701. doi: 10.1128/jvi.68.6.3693-3701.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Knipe D. M., Senechek D., Rice S. A., Smith J. L. Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4. J Virol. 1987 Feb;61(2):276–284. doi: 10.1128/jvi.61.2.276-284.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Koken M. H., Linares-Cruz G., Quignon F., Viron A., Chelbi-Alix M. K., Sobczak-Thépot J., Juhlin L., Degos L., Calvo F., de Thé H. The PML growth-suppressor has an altered expression in human oncogenesis. Oncogene. 1995 Apr 6;10(7):1315–1324. [PubMed] [Google Scholar]
  28. Koken M. H., Puvion-Dutilleul F., Guillemin M. C., Viron A., Linares-Cruz G., Stuurman N., de Jong L., Szostecki C., Calvo F., Chomienne C. The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J. 1994 Mar 1;13(5):1073–1083. doi: 10.1002/j.1460-2075.1994.tb06356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Korioth F., Gieffers C., Maul G. G., Frey J. Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment. J Cell Biol. 1995 Jul;130(1):1–13. doi: 10.1083/jcb.130.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Liptak L. M., Uprichard S. L., Knipe D. M. Functional order of assembly of herpes simplex virus DNA replication proteins into prereplicative site structures. J Virol. 1996 Mar;70(3):1759–1767. doi: 10.1128/jvi.70.3.1759-1767.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lukonis C. J., Weller S. K. Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication. J Virol. 1996 Mar;70(3):1751–1758. doi: 10.1128/jvi.70.3.1751-1758.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. MacArthur H., Walter G. Monoclonal antibodies specific for the carboxy terminus of simian virus 40 large T antigen. J Virol. 1984 Nov;52(2):483–491. doi: 10.1128/jvi.52.2.483-491.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Malik A. K., Martinez R., Muncy L., Carmichael E. P., Weller S. K. Genetic analysis of the herpes simplex virus type 1 UL9 gene: isolation of a LacZ insertion mutant and expression in eukaryotic cells. Virology. 1992 Oct;190(2):702–715. doi: 10.1016/0042-6822(92)90908-8. [DOI] [PubMed] [Google Scholar]
  34. Malik A. K., Shao L., Shanley J. D., Weller S. K. Intracellular localization of the herpes simplex virus type-1 origin binding protein, UL9. Virology. 1996 Oct 15;224(2):380–389. doi: 10.1006/viro.1996.0545. [DOI] [PubMed] [Google Scholar]
  35. Maul G. G., Guldner H. H., Spivack J. G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol. 1993 Dec;74(Pt 12):2679–2690. doi: 10.1099/0022-1317-74-12-2679. [DOI] [PubMed] [Google Scholar]
  36. Maul G. G., Ishov A. M., Everett R. D. Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1. Virology. 1996 Mar 1;217(1):67–75. doi: 10.1006/viro.1996.0094. [DOI] [PubMed] [Google Scholar]
  37. Maul G. G., Yu E., Ishov A. M., Epstein A. L. Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress. J Cell Biochem. 1995 Dec;59(4):498–513. doi: 10.1002/jcb.240590410. [DOI] [PubMed] [Google Scholar]
  38. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
  39. Moran E. Interaction of adenoviral proteins with pRB and p53. FASEB J. 1993 Jul;7(10):880–885. doi: 10.1096/fasebj.7.10.8344487. [DOI] [PubMed] [Google Scholar]
  40. Mu Z. M., Chin K. V., Liu J. H., Lozano G., Chang K. S. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol. 1994 Oct;14(10):6858–6867. doi: 10.1128/mcb.14.10.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Murphy M., Schenk P., Lankinen H. M., Cross A. M., Taylor P., Owsianka A., Hope R. G., Ludwig H., Marsden H. S. Mapping of epitopes on the 65k DNA-binding protein of herpes simplex virus type 1. J Gen Virol. 1989 Sep;70(Pt 9):2357–2364. doi: 10.1099/0022-1317-70-9-2357. [DOI] [PubMed] [Google Scholar]
  42. Olivo P. D., Nelson N. J., Challberg M. D. Herpes simplex virus DNA replication: the UL9 gene encodes an origin-binding protein. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5414–5418. doi: 10.1073/pnas.85.15.5414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Olivo P. D., Nelson N. J., Challberg M. D. Herpes simplex virus type 1 gene products required for DNA replication: identification and overexpression. J Virol. 1989 Jan;63(1):196–204. doi: 10.1128/jvi.63.1.196-204.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Quinlan M. P., Chen L. B., Knipe D. M. The intranuclear location of a herpes simplex virus DNA-binding protein is determined by the status of viral DNA replication. Cell. 1984 Apr;36(4):857–868. doi: 10.1016/0092-8674(84)90035-7. [DOI] [PubMed] [Google Scholar]
  45. Randall R. E., Dinwoodie N. Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol. 1986 Oct;67(Pt 10):2163–2177. doi: 10.1099/0022-1317-67-10-2163. [DOI] [PubMed] [Google Scholar]
  46. Rice S. A., Long M. C., Lam V., Spencer C. A. RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection. J Virol. 1994 Feb;68(2):988–1001. doi: 10.1128/jvi.68.2.988-1001.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Showalter S. D., Zweig M., Hampar B. Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun. 1981 Dec;34(3):684–692. doi: 10.1128/iai.34.3.684-692.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Skaliter R., Lehman I. R. Rolling circle DNA replication in vitro by a complex of herpes simplex virus type 1-encoded enzymes. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10665–10669. doi: 10.1073/pnas.91.22.10665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Szekely L., Pokrovskaja K., Jiang W. Q., de The H., Ringertz N., Klein G. The Epstein-Barr virus-encoded nuclear antigen EBNA-5 accumulates in PML-containing bodies. J Virol. 1996 Apr;70(4):2562–2568. doi: 10.1128/jvi.70.4.2562-2568.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Uprichard S. L., Knipe D. M. Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes. J Virol. 1996 Mar;70(3):1969–1980. doi: 10.1128/jvi.70.3.1969-1980.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Weis K., Rambaud S., Lavau C., Jansen J., Carvalho T., Carmo-Fonseca M., Lamond A., Dejean A. Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell. 1994 Jan 28;76(2):345–356. doi: 10.1016/0092-8674(94)90341-7. [DOI] [PubMed] [Google Scholar]
  52. Weller S. K., Lee K. J., Sabourin D. J., Schaffer P. A. Genetic analysis of temperature-sensitive mutants which define the gene for the major herpes simplex virus type 1 DNA-binding protein. J Virol. 1983 Jan;45(1):354–366. doi: 10.1128/jvi.45.1.354-366.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. 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]
  54. Wilcock D., Lane D. P. Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells. Nature. 1991 Jan 31;349(6308):429–431. doi: 10.1038/349429a0. [DOI] [PubMed] [Google Scholar]
  55. Wong S. W., Schaffer P. A. Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function. J Virol. 1991 May;65(5):2601–2611. doi: 10.1128/jvi.65.5.2601-2611.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wu C. A., Nelson N. J., McGeoch D. J., Challberg M. D. Identification of herpes simplex virus type 1 genes required for origin-dependent DNA synthesis. J Virol. 1988 Feb;62(2):435–443. doi: 10.1128/jvi.62.2.435-443.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Zhu Z., Cai W., Schaffer P. A. Cooperativity among herpes simplex virus type 1 immediate-early regulatory proteins: ICP4 and ICP27 affect the intracellular localization of ICP0. J Virol. 1994 May;68(5):3027–3040. doi: 10.1128/jvi.68.5.3027-3040.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. de Bruyn Kops A., Knipe D. M. Preexisting nuclear architecture defines the intranuclear location of herpesvirus DNA replication structures. J Virol. 1994 Jun;68(6):3512–3526. doi: 10.1128/jvi.68.6.3512-3526.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES