Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Dec;71(12):9442–9449. doi: 10.1128/jvi.71.12.9442-9449.1997

The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34.

S M Brown 1, A R MacLean 1, E A McKie 1, J Harland 1
PMCID: PMC230249  PMID: 9371605

Abstract

The herpes simplex virus (HSV) virulence factor ICP34.5, the mouse myeloid differentiation protein MyD116, and the hamster growth arrest and DNA damage protein GADD34 share a 63-amino-acid carboxyl domain which has significant homologies to otherwise divergent proteins. Here we report that both ICP34.5 and its cellular homolog MyD116 complex through the conserved domain with proliferating cell nuclear antigen. In addition, HSV infection induces a novel 70-kDa cellular protein detectable by antisera to both ICP34.5 and GADD34, demonstrating that this novel protein possesses homology with the 63-amino-acid conserved domain.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

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

  1. Ackermann M., Chou J., Sarmiento M., Lerner R. A., Roizman B. Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome. J Virol. 1986 Jun;58(3):843–850. doi: 10.1128/jvi.58.3.843-850.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bravo R., Frank R., Blundell P. A., Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987 Apr 2;326(6112):515–517. doi: 10.1038/326515a0. [DOI] [PubMed] [Google Scholar]
  3. Brown S. M., Harland J., MacLean A. R., Podlech J., Clements J. B. Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2. J Gen Virol. 1994 Sep;75(Pt 9):2367–2377. doi: 10.1099/0022-1317-75-9-2367. [DOI] [PubMed] [Google Scholar]
  4. Brown S. M., MacLean A. R., Aitken J. D., Harland J. ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro. J Gen Virol. 1994 Dec;75(Pt 12):3679–3686. doi: 10.1099/0022-1317-75-12-3679. [DOI] [PubMed] [Google Scholar]
  5. Brown S. M., Ritchie D. A., Subak-Sharpe J. H. Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. J Gen Virol. 1973 Mar;18(3):329–346. doi: 10.1099/0022-1317-18-3-329. [DOI] [PubMed] [Google Scholar]
  6. Chen I. T., Smith M. L., O'Connor P. M., Fornace A. J., Jr Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA. Oncogene. 1995 Nov 16;11(10):1931–1937. [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Chou J., Chen J. J., Gross M., Roizman B. Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 134.5- mutants of herpes simplex virus 1. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10516–10520. doi: 10.1073/pnas.92.23.10516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chou J., Kern E. R., Whitley R. J., Roizman B. Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science. 1990 Nov 30;250(4985):1262–1266. doi: 10.1126/science.2173860. [DOI] [PubMed] [Google Scholar]
  10. Chou J., Roizman B. Herpes simplex virus 1 gamma(1)34.5 gene function, which blocks the host response to infection, maps in the homologous domain of the genes expressed during growth arrest and DNA damage. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5247–5251. doi: 10.1073/pnas.91.12.5247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chou J., Roizman B. The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3266–3270. doi: 10.1073/pnas.89.8.3266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chou J., Roizman B. The terminal a sequence of the herpes simplex virus genome contains the promoter of a gene located in the repeat sequences of the L component. J Virol. 1986 Feb;57(2):629–637. doi: 10.1128/jvi.57.2.629-637.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dolan A., McKie E., MacLean A. R., McGeoch D. J. Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17. J Gen Virol. 1992 Apr;73(Pt 4):971–973. doi: 10.1099/0022-1317-73-4-971. [DOI] [PubMed] [Google Scholar]
  14. Fenwick M. L., Everett R. D. Inactivation of the shutoff gene (UL41) of herpes simplex virus types 1 and 2. J Gen Virol. 1990 Dec;71(Pt 12):2961–2967. doi: 10.1099/0022-1317-71-12-2961. [DOI] [PubMed] [Google Scholar]
  15. Flores-Rozas H., Kelman Z., Dean F. B., Pan Z. Q., Harper J. W., Elledge S. J., O'Donnell M., Hurwitz J. Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8655–8659. doi: 10.1073/pnas.91.18.8655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fornace A. J., Jr, Nebert D. W., Hollander M. C., Luethy J. D., Papathanasiou M., Fargnoli J., Holbrook N. J. Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. Mol Cell Biol. 1989 Oct;9(10):4196–4203. doi: 10.1128/mcb.9.10.4196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Harland J., Brown S. M. Isolation and characterization of deletion mutants of herpes simplex virus type 2 (strain HG52). J Gen Virol. 1985 Jun;66(Pt 6):1305–1321. doi: 10.1099/0022-1317-66-6-1305. [DOI] [PubMed] [Google Scholar]
  18. He B., Chou J., Liebermann D. A., Hoffman B., Roizman B. The carboxyl terminus of the murine MyD116 gene substitutes for the corresponding domain of the gamma(1)34.5 gene of herpes simplex virus to preclude the premature shutoff of total protein synthesis in infected human cells. J Virol. 1996 Jan;70(1):84–90. doi: 10.1128/jvi.70.1.84-90.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kesari S., Lee V. M., Brown S. M., Trojanowski J. Q., Fraser N. W. Selective vulnerability of mouse CNS neurons to latent infection with a neuroattenuated herpes simplex virus-1. J Neurosci. 1996 Sep 15;16(18):5644–5653. doi: 10.1523/JNEUROSCI.16-18-05644.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kesari S., Randazzo B. P., Valyi-Nagy T., Huang Q. S., Brown S. M., MacLean A. R., Lee V. M., Trojanowski J. Q., Fraser N. W. Therapy of experimental human brain tumors using a neuroattenuated herpes simplex virus mutant. Lab Invest. 1995 Nov;73(5):636–648. [PubMed] [Google Scholar]
  21. Kill I. R., Bridger J. M., Campbell K. H., Maldonado-Codina G., Hutchison C. J. The timing of the formation and usage of replicase clusters in S-phase nuclei of human diploid fibroblasts. J Cell Sci. 1991 Dec;100(Pt 4):869–876. doi: 10.1242/jcs.100.4.869. [DOI] [PubMed] [Google Scholar]
  22. Li R., Waga S., Hannon G. J., Beach D., Stillman B. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature. 1994 Oct 6;371(6497):534–537. doi: 10.1038/371534a0. [DOI] [PubMed] [Google Scholar]
  23. Lord K. A., Hoffman-Liebermann B., Liebermann D. A. Complexity of the immediate early response of myeloid cells to terminal differentiation and growth arrest includes ICAM-1, Jun-B and histone variants. Oncogene. 1990 Mar;5(3):387–396. [PubMed] [Google Scholar]
  24. MACPHERSON I., STOKER M. Polyoma transformation of hamster cell clones--an investigation of genetic factors affecting cell competence. Virology. 1962 Feb;16:147–151. doi: 10.1016/0042-6822(62)90290-8. [DOI] [PubMed] [Google Scholar]
  25. MacLean A. R., ul-Fareed M., Robertson L., Harland J., Brown S. M. Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the 'a' sequence. J Gen Virol. 1991 Mar;72(Pt 3):631–639. doi: 10.1099/0022-1317-72-3-631. [DOI] [PubMed] [Google Scholar]
  26. MacLean C. A., Efstathiou S., Elliott M. L., Jamieson F. E., McGeoch D. J. Investigation of herpes simplex virus type 1 genes encoding multiply inserted membrane proteins. J Gen Virol. 1991 Apr;72(Pt 4):897–906. doi: 10.1099/0022-1317-72-4-897. [DOI] [PubMed] [Google Scholar]
  27. Markovitz N. S., Baunoch D., Roizman B. The range and distribution of murine central nervous system cells infected with the gamma(1)34.5- mutant of herpes simplex virus 1. J Virol. 1997 Jul;71(7):5560–5569. doi: 10.1128/jvi.71.7.5560-5569.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marsden H. S., Crombie I. K., Subak-Sharpe J. H. Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature-sensitive mutants of HSV strain 17. J Gen Virol. 1976 Jun;31(3):347–372. doi: 10.1099/0022-1317-31-3-347. [DOI] [PubMed] [Google Scholar]
  29. McGeoch D. J., Barnett B. C. Neurovirulence factor. Nature. 1991 Oct 17;353(6345):609–609. doi: 10.1038/353609b0. [DOI] [PubMed] [Google Scholar]
  30. McKay E. M., McVey B., Marsden H. S., Brown S. M., MacLean A. R. The herpes simplex virus type 1 strain 17 open reading frame RL1 encodes a polypeptide of apparent M(r) 37K equivalent to ICP34.5 of herpes simplex virus type 1 strain F. J Gen Virol. 1993 Nov;74(Pt 11):2493–2497. doi: 10.1099/0022-1317-74-11-2493. [DOI] [PubMed] [Google Scholar]
  31. McKie E. A., Hope R. G., Brown S. M., MacLean A. R. Characterization of the herpes simplex virus type 1 strain 17+ neurovirulence gene RL1 and its expression in a bacterial system. J Gen Virol. 1994 Apr;75(Pt 4):733–741. doi: 10.1099/0022-1317-75-4-733. [DOI] [PubMed] [Google Scholar]
  32. McKie E. A., MacLean A. R., Lewis A. D., Cruickshank G., Rampling R., Barnett S. C., Kennedy P. G., Brown S. M. Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours--evaluation of a potentially effective clinical therapy. Br J Cancer. 1996 Sep;74(5):745–752. doi: 10.1038/bjc.1996.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Meredith M., Orr A., Everett R. Herpes simplex virus type 1 immediate-early protein Vmw110 binds strongly and specifically to a 135-kDa cellular protein. Virology. 1994 May 1;200(2):457–469. doi: 10.1006/viro.1994.1209. [DOI] [PubMed] [Google Scholar]
  34. Prelich G., Tan C. K., Kostura M., Mathews M. B., So A. G., Downey K. M., Stillman B. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature. 1987 Apr 2;326(6112):517–520. doi: 10.1038/326517a0. [DOI] [PubMed] [Google Scholar]
  35. Randazzo B. P., Kesari S., Gesser R. M., Alsop D., Ford J. C., Brown S. M., Maclean A., Fraser N. W. Treatment of experimental intracranial murine melanoma with a neuroattenuated herpes simplex virus 1 mutant. Virology. 1995 Aug 1;211(1):94–101. doi: 10.1006/viro.1995.1382. [DOI] [PubMed] [Google Scholar]
  36. Robertson L. M., MacLean A. R., Brown S. M. Peripheral replication and latency reactivation kinetics of the non-neurovirulent herpes simplex virus type 1 variant 1716. J Gen Virol. 1992 Apr;73(Pt 4):967–970. doi: 10.1099/0022-1317-73-4-967. [DOI] [PubMed] [Google Scholar]
  37. Shivji K. K., Kenny M. K., Wood R. D. Proliferating cell nuclear antigen is required for DNA excision repair. Cell. 1992 Apr 17;69(2):367–374. doi: 10.1016/0092-8674(92)90416-a. [DOI] [PubMed] [Google Scholar]
  38. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  39. Spivack J. G., Fareed M. U., Valyi-Nagy T., Nash T. C., O'Keefe J. S., Gesser R. M., McKie E. A., MacLean A. R., Fraser N. W., Brown S. M. Replication, establishment of latent infection, expression of the latency-associated transcripts and explant reactivation of herpes simplex virus type 1 gamma 34.5 mutants in a mouse eye model. J Gen Virol. 1995 Feb;76(Pt 2):321–332. doi: 10.1099/0022-1317-76-2-321. [DOI] [PubMed] [Google Scholar]
  40. Taha M. Y., Clements G. B., Brown S. M. A variant of herpes simplex virus type 2 strain HG52 with a 1.5 kb deletion in RL between 0 to 0.02 and 0.81 to 0.83 map units is non-neurovirulent for mice. J Gen Virol. 1989 Mar;70(Pt 3):705–716. doi: 10.1099/0022-1317-70-3-705. [DOI] [PubMed] [Google Scholar]
  41. Taha M. Y., Clements G. B., Brown S. M. The herpes simplex virus type 2 (HG52) variant JH2604 has a 1488 bp deletion which eliminates neurovirulence in mice. J Gen Virol. 1989 Nov;70(Pt 11):3073–3078. doi: 10.1099/0022-1317-70-11-3073. [DOI] [PubMed] [Google Scholar]
  42. Timbury M. C. Temperature-sensitive mutants of herpes simplex virus type 2. J Gen Virol. 1971 Nov;13(2):373–376. doi: 10.1099/0022-1317-13-2-373. [DOI] [PubMed] [Google Scholar]
  43. Waga S., Hannon G. J., Beach D., Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994 Jun 16;369(6481):574–578. doi: 10.1038/369574a0. [DOI] [PubMed] [Google Scholar]
  44. Warbrick E., Lane D. P., Glover D. M., Cox L. S. A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol. 1995 Mar 1;5(3):275–282. doi: 10.1016/s0960-9822(95)00058-3. [DOI] [PubMed] [Google Scholar]
  45. Zhan Q., Lord K. A., Alamo I., Jr, Hollander M. C., Carrier F., Ron D., Kohn K. W., Hoffman B., Liebermann D. A., Fornace A. J., Jr The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol Cell Biol. 1994 Apr;14(4):2361–2371. doi: 10.1128/mcb.14.4.2361. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES