1887

Abstract

Bovine herpesvirus 1 (BHV-1) infected-cell protein 0 (bICP0) stimulates productive infection by activating viral gene expression. In this study, an attempt was made to construct a recombinant virus with point mutations in the CHC zinc RING finger of bICP0, as this domain is necessary for activating viral transcription and productive infection. A virus was identified in bovine cells that induced small clusters of infected cells resembling a small plaque. Instead of the expected mutations within the zinc RING finger, this virus contained a point mutation within the initiating ATG of bICP0, a point mutation two bases downstream from the ATG mutation and deletion of flanking plasmid sequences used for homologous recombination. The bICP0 mutant was rescued with wild-type (wt) bICP0 sequences and the bICP0-rescued virus produced wt plaques. The bICP0-rescued virus and wt BHV-1, but not the mutant, expressed the bICP0 protein during productive infection of bovine cells, suggesting that the mutant virus was a null mutant. Consequently, the mutant was designated the bICP0 null mutant. Infection of bovine cells with the bICP0 null mutant resulted in at least 100-fold lower virus titres, indicating that bICP0 protein expression is important, but not required, for virus production. When bovine cells infected with the bICP0 null mutant virus were subcultured, the cells continued to divide, but viral DNA could be detected after more than 35 passages, suggesting that the bICP0 null mutant induced a persistent-like infection in bovine cells and that it may be useful for generating additional bICP0 mutants.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80921-0
2005-07-01
2024-12-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/7/vir861987.html?itemId=/content/journal/jgv/10.1099/vir.0.80921-0&mimeType=html&fmt=ahah

References

  1. Abril C., Engels M., Liman A., Hilbe M., Albini S., Franchini M., Suter M., Ackermann M. 2004; Both viral and host factors contribute to neurovirulence of bovine herpesviruses 1 and 5 in interferon receptor-deficient mice. J Virol 78:3644–3653 [CrossRef]
    [Google Scholar]
  2. Boutell C., Sadis S., Everett R. D. 2002; Herpes simplex virus type 1 immediate-early protein ICP0 and its isolated RING finger domain act as ubiquitin E3 ligases in vitro. J Virol 76:841–850 [CrossRef]
    [Google Scholar]
  3. Carter J. J., Weinberg A. D., Pollard A., Reeves R., Magnuson J. A., Magnuson N. S. 1989; Inhibition of T-lymphocyte mitogenic responses and effects on cell functions by bovine herpesvirus 1. J Virol 63:1525–1530
    [Google Scholar]
  4. Devireddy L. R., Jones C. J. 1999; Activation of caspases and p53 by bovine herpesvirus 1 infection results in programmed cell death and efficient virus release. J Virol 73:3778–3788
    [Google Scholar]
  5. Everett R. D. 1987; A detailed mutational analysis of Vmw110, a trans -acting transcriptional activator encoded by herpes simplex virus type 1. EMBO J 6:2069–2076
    [Google Scholar]
  6. Everett R. D. 1988; Analysis of the functional domains of herpes simplex virus type 1 immediate-early polypeptide Vmw110. J Mol Biol 202:87–96 [CrossRef]
    [Google Scholar]
  7. Everett R. D., Barlow P., Milner A., Luisi B., Orr A., Hope G., Lyon D. 1993; A novel arrangement of zinc-binding residues and secondary structure in the C3HC4 motif of an alpha herpes virus protein family. J Mol Biol 234:1038–1047 [CrossRef]
    [Google Scholar]
  8. Everett R. D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J. 1997; A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J 16:1519–1530 [CrossRef]
    [Google Scholar]
  9. Everett R. D., Earnshaw W. C., Findlay J., Lomonte P. 1999a; Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. EMBO J 18:1526–1538 [CrossRef]
    [Google Scholar]
  10. Everett R. D., Lomonte P., Sternsdorf T., van Driel R., Orr A. 1999b; Cell cycle regulation of PML modification and ND10 composition. J Cell Sci 112:4581–4588
    [Google Scholar]
  11. Favoreel H. W., Nauwynck H. J., Pensaert M. B. 2000; Immunological hiding of herpesvirus-infected cells. Arch Virol 145:1269–1290 [CrossRef]
    [Google Scholar]
  12. Fraefel C., Zeng J., Choffat Y., Engels M., Schwyzer M., Ackermann M. 1994; Identification and zinc dependence of the bovine herpesvirus 1 transactivator protein BICP0. J Virol 68:3154–3162
    [Google Scholar]
  13. Fuchs M., Hübert P., Detterer J., Rziha H.-J. 1999; Detection of bovine herpesvirus type 1 in blood from naturally infected cattle by using a sensitive PCR that discriminates between wild-type virus and virus lacking glycoprotein E. J Clin Microbiol 37:2498–2507
    [Google Scholar]
  14. Geiser V. 2001; Regulation of productive bovine herpesvirus 1 infection by bICP0, latency related gene, and pocket proteins, and E2F family members . MSc thesis University of Nebraska-Lincoln; NE, USA:
  15. Geiser V., Jones C. 2003; Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4. J Gen Virol 84:929–938 [CrossRef]
    [Google Scholar]
  16. Hanon E., Vanderplasschen A., Lyaku S., Keil G., Denis M., Pastoret P.-P. 1996; Inactivated bovine herpesvirus 1 induces apoptotic cell death of mitogen-stimulated bovine peripheral blood mononuclear cells. J Virol 70:4116–4120
    [Google Scholar]
  17. Hanon E., Hoornaert S., Dequiedt F., Vanderplasschen A., Lyaku J., Willems L., Pastoret P.-P. 1997; Bovine herpesvirus 1-induced apoptosis occurs at the G0/G1 phase of the cell cycle. Virology 232:351–358 [CrossRef]
    [Google Scholar]
  18. Hanon E., Meyer G., Vanderplasschen A., Dessy-Doizé C., Thiry E., Pastoret P.-P. 1998; Attachment but not penetration of bovine herpesvirus 1 is necessary to induce apoptosis in target cells. J Virol 72:7638–7641
    [Google Scholar]
  19. Hanon E., Keil G., van Drunen Little-van den Hurk S., Griebel P., Vanderplasschen A., Rijsewijk F. A. M., Babiuk L., Pastoret P.-P. 1999; Bovine herpesvirus 1-induced apoptotic cell death: role of glycoprotein D. Virology 257:191–197 [CrossRef]
    [Google Scholar]
  20. Hariharan M. J., Nataraj C., Srikumaran S. 1993; Down regulation of murine MHC class I expression by bovine herpesvirus 1. Viral Immunol 6:273–284 [CrossRef]
    [Google Scholar]
  21. Henderson G., Zhang Y., Inman M., Jones D., Jones C. 2004; Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells. J Gen Virol 85:3511–3516 [CrossRef]
    [Google Scholar]
  22. Hobbs W. E. II, DeLuca N. A. 1999; Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0. J Virol 73:8245–8255
    [Google Scholar]
  23. Hossain A., Schang L. M., Jones C. 1995; Identification of gene products encoded by the latency-related gene of bovine herpesvirus 1. J Virol 69:5345–5352
    [Google Scholar]
  24. Inman M., Lovato L., Doster A., Jones C. 2001a; A mutation in the latency-related gene of bovine herpesvirus 1 leads to impaired ocular shedding in acutely infected calves. J Virol 75:8507–8515 [CrossRef]
    [Google Scholar]
  25. Inman M., Zhang Y., Geiser V., Jones C. 2001b; The zinc ring finger in the bICP0 protein encoded by bovine herpesvirus-1 mediates toxicity and activates productive infection. J Gen Virol 82:483–492
    [Google Scholar]
  26. Jones C. 1998; Alphaherpesvirus latency: its role in disease and survival of the virus in nature. Adv Virus Res 51:81–133
    [Google Scholar]
  27. Jones C. 2003; Herpes simplex virus type 1 and bovine herpesvirus 1 latency. Clin Microbiol Rev 16:79–95 [CrossRef]
    [Google Scholar]
  28. Katze M. G., He Y., Gale M. Jr 2002; Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2:675–687 [CrossRef]
    [Google Scholar]
  29. Koppel R., Fraefel C., Vogt B., Bello L. J., Lawrence W. C., Schwyzer M. 1996; Recombinant bovine herpesvirus-1 (BHV-1) lacking transactivator protein BICP0 entails lack of glycoprotein C and severely reduced infectivity. Biol Chem 377:787–795
    [Google Scholar]
  30. Lomonte P., Everett R. D. 1999; Herpes simplex virus type 1 immediate-early protein Vmw110 inhibits progression of cells through mitosis and from G1 into S phase of the cell cycle. J Virol 73:9456–9467
    [Google Scholar]
  31. Maul G. G., Everett R. D. 1994; The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0. J Gen Virol 75:1223–1233 [CrossRef]
    [Google Scholar]
  32. Maul G. G., Guldner H. H., Spivack J. G. 1993; Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0. J Gen Virol 74:2679–2690 [CrossRef]
    [Google Scholar]
  33. Mossman K. L., Smiley J. R. 2002; Herpes simplex virus ICP0 and ICP34.5 counteract distinct interferon-induced barriers to virus replication. J Virol 76:1995–1998 [CrossRef]
    [Google Scholar]
  34. Mossman K. L., Saffran H. A., Smiley J. R. 2000; Herpes simplex virus ICP0 mutants are hypersensitive to interferon. J Virol 74:2052–2056 [CrossRef]
    [Google Scholar]
  35. Mossman K. L., Macgregor P. F., Rozmus J. J., Goryachev A. B., Edwards A. M., Smiley J. R. 2001; Herpes simplex virus triggers and then disarms a host antiviral response. J Virol 75:750–758 [CrossRef]
    [Google Scholar]
  36. Mweene A. S., Okazaki K., Kida H. 1996; Detection of viral genome in non-neural tissues of cattle experimentally infected with bovine herpesvirus 1. Jpn J Vet Res 44:165–174
    [Google Scholar]
  37. Nataraj C., Eidmann S., Hariharan M. J., Sur J. H., Perry G. A., Srikumaran S. 1997; Bovine herpesvirus 1 downregulates the expression of bovine MHC class I molecules. Viral Immunol 10:21–34 [CrossRef]
    [Google Scholar]
  38. Parkinson J., Everett R. D. 2000; Alphaherpesvirus proteins related to herpes simplex virus type 1 ICP0 affect cellular structures and proteins. J Virol 74:10006–10017 [CrossRef]
    [Google Scholar]
  39. Rock D., Lokensgard J., Lewis T., Kutish G. 1992; Characterization of dexamethasone-induced reactivation of latent bovine herpesvirus 1. J Virol 66:2484–2490
    [Google Scholar]
  40. Sacks W. R., Schaffer P. A. 1987; Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture. J Virol 61:829–839
    [Google Scholar]
  41. Samaniego L. A., Neiderhiser L., DeLuca N. A. 1998; Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins. J Virol 72:3307–3320
    [Google Scholar]
  42. Schang L. M., Jones C. 1997; Analysis of bovine herpesvirus 1 transcripts during a primary infection of trigeminal ganglia of cattle. J Virol 71:6786–6795
    [Google Scholar]
  43. Stow N. D., Stow E. C. 1986; Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol 67:2571–2585 [CrossRef]
    [Google Scholar]
  44. Van Sant C., Hagglund R., Lopez P., Roizman B. 2001; The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A 98:8815–8820 [CrossRef]
    [Google Scholar]
  45. Winkler M. T. C., Doster A., Jones C. 1999; Bovine herpesvirus 1 can infect CD4+ T lymphocytes and induce programmed cell death during acute infection of cattle. J Virol 73:8657–8668
    [Google Scholar]
  46. Winkler M. T. C., Doster A., Jones C. 2000; Persistence and reactivation of bovine herpesvirus 1 in the tonsils of latently infected calves. J Virol 74:5337–5346 [CrossRef]
    [Google Scholar]
  47. Winkler M. T. C., Doster A., Sur J.-H., Jones C. 2002; Analysis of bovine trigeminal ganglia following infection with bovine herpesvirus 1. Vet Microbiol 86:139–155 [CrossRef]
    [Google Scholar]
  48. Wirth U. V., Gunkel K., Engels M., Schwyzer M. 1989; Spatial and temporal distribution of bovine herpesvirus 1 transcripts. J Virol 63:4882–4889
    [Google Scholar]
  49. Wirth U. V., Vogt B., Schwyzer M. 1991; The three major immediate-early transcripts of bovine herpesvirus 1 arise from two divergent and spliced transcription units. J Virol 65:195–205
    [Google Scholar]
  50. Wirth U. V., Fraefel C., Vogt B., Vlček Č., Pačes V., Schwyzer M. 1992; Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3′ coterminal and encode a putative zinc finger transactivator protein. J Virol 66:2763–2772
    [Google Scholar]
  51. Yao F., Schaffer P. A. 1995; An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1. J Virol 69:6249–6258
    [Google Scholar]
  52. Zhang Y., Jones C. 2001; The bovine herpesvirus 1 immediate-early protein (bICP0) associates with histone deacetylase 1 to activate transcription. J Virol 75:9571–9578 [CrossRef]
    [Google Scholar]
  53. Zhang Y., Zhou J., Jones C. 2005; Identification of functional domains within the bICP0 protein encoded by bovine herpesvirus 1. J Gen Virol 86:879–886 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.80921-0
Loading
/content/journal/jgv/10.1099/vir.0.80921-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error