The bovine herpesvirus 1 gene encoding infected cell protein 0 (bICP0) can inhibit interferon-dependent transcription in the absence of other viral genes

Gail Henderson, Yange Zhang and Clinton Jones

Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA

Correspondence
Clinton Jones
cjones{at}unlnotes.unl.edu


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The infected cell protein 0 (bICP0) encoded by Bovine herpesvirus 1 (BHV-1) stimulates viral gene expression and productive infection. As bICP0 is expressed constitutively during productive infection, it is considered to be the major viral regulatory protein. Like other alphaherpesvirus ICP0 homologues, bICP0 contains a zinc RING finger near its N terminus that activates transcription and regulates subcellular localization. In this study, evidence is provided that bICP0 represses the human beta interferon (IFN-{beta}) promoter and a simple promoter with consensus IFN-stimulated response elements following stimulation with double-stranded RNA (polyinosinic–polycytidylic acid), IFN regulatory factor 3 (IRF3) or IRF7. bICP0 also inhibits the ability of two protein kinases (TBK1 and IKK{varepsilon}) to activate IFN-{beta} promoter activity. The zinc RING finger is necessary for inhibiting IFN-dependent transcription in certain cell types. Collectively, these studies suggest that bICP0 activates productive infection by stimulating viral gene expression and inhibiting IFN-dependent transcription.

Supplementary tables showing regulation of the IFN-{beta} promoter by IKK{varepsilon} and TBK1 and regulation of ISRE-dependent transcription by bICP0 are available in JGV Online.


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Infection of cattle with Bovine herpesvirus 1 (BHV-1) leads to conjunctivitis, pneumonia, genital disorders, abortions and ‘shipping fever’, an upper-respiratory infection (Tikoo et al., 1995). Infection of bovine cells causes rapid cell death and an increase in apoptosis (Devireddy & Jones, 1999). Viral gene expression during productive infection is regulated temporally in three phases: immediate-early (IE), early (E) and late (L) (Jones, 2003).

The bICP0 protein activates viral gene expression and is encoded by IE transcription unit 1 (IEtu1) (Wirth et al., 1992; Everett, 2000). bICP0 RNA is expressed constitutively during productive infection because the gene has an IE and E promoter (Fraefel et al., 1994). bICP0 (Fig. 1a) and herpes simplex virus type 1 (HSV-1) ICP0 proteins contain a well-conserved C3HC4 zinc RING finger, near their respective N termini, that is crucial for transcriptional activation (Everett, 1987, 1988; Everett et al., 1993; Inman et al., 2001). ICP0 (Maul et al., 1993; Maul & Everett, 1994; Everett et al., 1997, 1999a, b) and bICP0 (Parkinson & Everett, 2000; Inman et al., 2001) colocalize with and disrupt the promyelocytic leukaemia protein-containing nuclear domains (ND10 or PODS).



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Fig. 1. Regulation of IFN-{beta} promoter activity by bICP0. (a) bICP0 contains two transcriptional-activation domains (TAD), a zinc RING finger (Wirth et al., 1992), an acidic domain and a nuclear-localization signal (NLS) (Zhang et al., 2005). The SalI site was used to construct the {Delta}bICP0 construct. Two amino acids were mutated in the bICP0 zinc RING finger: aa 13 was changed from C to G and aa 51 from C to A (13G/51A) (Inman et al., 2001). The bICP0 constructs contain the SV40 poly(A) addition site at the 3' terminus of the bICP0 insert. Numbers denote amino acid positions. (b) Approximately 1x105 neuro-2A cells in a 60 mm dish were transfected with 1 µg IFN-{beta} promoter (Zhang et al., 2005). Certain cultures were also cotransfected with 1, 2 or 3 µg of the wt bICP0 construct or a plasmid containing the BHV-1 LR gene. All cultures were transfected with 50 µg poly(IC) ml–1. (c) Neuro-2A cells (approx. 1x105 cells in a 60 mm dish) were transfected with 1 µg IFN-{beta} promoter. Some cultures were cotransfected with 1, 2 or 3 µg wt bICP0 construct and 2 µg IRF3 or IRF7, which yielded maximal stimulation of IFN-{beta} promoter activity. Increasing concentrations of wt bICP0 constructs were also transfected with 1 µg LR promoter CAT construct (p0.95cat/1) (Jones et al., 1990). Plasmid DNA was maintained at the same concentration by including a blank expression vector (pcDNA3.1). At 40 h after transfection, cell lysate was prepared by three freeze–thaw cycles in 0·25 M Tris (pH 8·0). CAT activity was measured in the presence of 0·2 µCi (7·4 kBq) [14C]chloramphenicol and 0·5 mM acetyl-coenzyme A (Inman et al., 2001; Zhang & Jones, 2001). The amount of acetylated chloramphenicol was measured with a Bio-Rad Molecular Imager FX following separation by thin-layer chromatography. Basal values for the IFN-{beta} promoter were normalized to 1 and other values are presented as fold activation relative to basal promoter levels. Results are means of at least three experiments.

 
bICP0 associates with histone deacetylase 1 (HDAC1) and can relieve HDAC1-mediated transcriptional repression (Zhang & Jones, 2001). When BHV-1 DNA is transfected into permissive cells, plaque formation is inefficient unless bICP0, HSV-1 ICP0, the adenovirus E1A gene or E2F4 is included in the transfection mix (Inman et al., 2001; Geiser & Jones, 2003). The E1A protein (Chakravarti et al., 1999; Hamamori et al., 1999), E2F4 (Attwooll et al., 2004) and bICP0 (Zhang & Jones, 2001) interact with HDAC1-containing complexes, suggesting that sequestering HDAC1 stimulates BHV-1 productive infection.

HSV-1 infection of cultured human cells induces interferon (IFN) production. ICP0, ICP34·5 and Us11 are the known viral genes that inhibit IFN activation after infection (Mossman et al., 2000, 2001; Mossman & Smiley, 2002; Peters et al., 2002; Lin et al., 2004). The viral glycoprotein gD induces IFN-{alpha} production in mononuclear cells, leading to IFN response factor 3 (IRF3) activation (Katze et al., 2002). Mice lacking type I and type II IFN receptors in combination with RAG-2 gene deletions die within a few days of BHV-1 infection, whereas infection of wild-type (wt) mice does not lead to clinical symptoms (Abril et al., 2004). To date, the BHV-1 genes that regulate IFN have not been identified.

To test whether bICP0 inhibited IFN-dependent transcription in the absence of other viral genes, transient-transfection assays were performed using a wt bICP0 construct, a zinc RING finger mutant (13G/51A) or a deletion mutant that lacks the last 320 aa of bICP0 ({Delta}bICP0) (Fig. 1a). These constructs express similar levels of bICP0 in transiently transfected cells (Zhang & Jones, 2001; Henderson et al., 2004; Zhang et al., 2005). We predicted that bICP0 regulates IFN-dependent transcription because HSV-1 ICP0 inhibits IFN-dependent transcription (Mossman et al., 2000, 2001; Mossman & Smiley, 2002; Lin et al., 2004). Except for the zinc RING finger located near the N terminus of bICP0 (Fig. 1b), there is little similarity between bICP0 and ICP0, making it necessary to test formally whether bICP0 inhibits IFN-dependent transcription.

The IFN-{beta} promoter was initially tested because it is activated strongly by early events that occur following virus infection (Katze et al., 2002). For these studies, a plasmid containing the human IFN-{beta} promoter (–110 to +20) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene was used. This promoter construct was obtained from Dr Stavros Lomvardas (Columbia University, NY, USA) and it contains elements that are activated by virus infection (Munshi et al., 2001). As reported previously (Peng et al., 2005), IFN-{beta} promoter activity was low in mouse neuroblastoma cells (neuro-2A cells) (Fig. 1b). Double-stranded RNA [polyinosinic–polycytidylic acid, poly(IC)] increased IFN-{beta} promoter activity by more than 11-fold in neuro-2A cells (Fig. 1b). bICP0 decreased IFN-{beta} promoter activity in a dose-dependent manner and at the highest concentration of bICP0 tested, IFN-{beta} promoter activity was reduced by approximately 10-fold. We also tested a plasmid that expresses the latency-related (LR) gene products because the LR gene overlaps bICP0 (Jones, 2003). LR gene products were unable to inhibit IFN-{beta} promoter activity in transiently transfected neuro-2A cells (Fig. 1b).

IRF3 and IRF7 are transcription factors that are activated by phosphorylation following IFN induction (Barnes et al., 2002). Overexpression of IRF3 or IRF7 consistently stimulated IFN-{beta} promoter activity by more than five- or sevenfold, respectively, in neuro-2A cells (Fig. 1c). With as little as 1 µg bICP0 added to the cotransfection mix, IFN-{beta} promoter activity was reduced by more than twofold when activated by IRF3 and by fivefold when activated by IRF7 (Fig. 1c). When bICP0 was cotransfected with a BHV-1 LR promoter construct, bICP0 activated LR promoter activity by more than sevenfold, which confirmed the results of earlier studies (Bratanich & Jones, 1992). These studies indicated that bICP0 inhibited IFN-{beta} promoter activity, but activated LR promoter activity in transiently transfected neuro-2A cells.

IRF3 is activated by phosphorylation in two steps (Barnes et al., 2002; Sarkar et al., 2004) and two protein kinases, IKK{varepsilon} and TBK1, coordinate IRF3 activation (Fitzgerald et al., 2003; Sharma et al., 2003). Cytomegalovirus expression plasmids containing these protein kinases were obtained from Dr Tom Maniatis (Harvard University, MA, USA). IKK{varepsilon} consistently activated IFN-{beta} promoter activity in neuro-2A cells by more than sevenfold (Fig. 2a and Supplementary Table S1a, available in JGV Online). wt bICP0 or the {Delta}bICP0 mutant reduced IFN-{beta} promoter activity by approximately 50 % using 1 µg bICP0, and repression occurred in a dose-dependent fashion. At the higher concentration of bICP0 (wt or {Delta}bICP0), activation of IFN-{beta} promoter activity by IKK{varepsilon} was negated. In contrast, the 13G/51A zinc RING finger mutant was unable to inhibit IFN-{beta} promoter activity to basal levels. Similar results were obtained in human 293 cells (data not shown).



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Fig. 2. Regulation of the IFN-{beta} promoter by IKK{varepsilon} and TBK1. (a) Neuro-2A cells (approx. 1x105 cells in a 60 mm dish) were transfected with 1 µg IFN-{beta} CAT construct, 2 µg IKK{varepsilon} and the designated bICP0 plasmids (1, 2 or 3 µg). (b) Approximately 1x105 293 cells in a 60 mm dish were transfected with 1 µg IFN-{beta} CAT construct, 2 µg TBK1 and the designated bICP0 plasmids (1, 2 or 3 µg). CAT activity was measured as described in the legend to Fig. 1. The amounts of IKK{varepsilon} and TBK1 used for this study were optimal for activating the IFN-{beta} promoter. Results are means of four independent experiments.

 
Although TBK1 did not stimulate IFN-{beta} promoter activity in neuro-2A cells, TBK1 stimulated IFN-{beta} promoter activity by 2·7-fold in human epithelial cells (293) (Fig. 2b and Supplementary Table S1b). Induction of IFN-{beta} promoter activity by TBK1 was repressed to basal levels by wt bICP0 or {Delta}bICP0, but not by the 13G/51A construct.

Activated IRF3 induces expression of IFN-{alpha}4 in mice or IFN-{alpha}1 in humans, and IRF3 cooperates with other transcription factors to activate the IFN-{beta} promoter (Fitzgerald et al., 2003; Sharma et al., 2003; Sarkar et al., 2004). Transcription of other IFN-{alpha} subtypes requires IRF7, which is crucial for type I IFN-dependent immune responses in mice (Honda et al., 2005). IFN-stimulated response elements (ISREs) are present in many genes activated by IFN and are necessary for IFN induction. Consequently, we tested whether bICP0 inhibited ISRE-dependent transcription.

We subsequently tested whether bICP0 inhibited a minimal human immunodeficiency virus promoter construct with four consensus ISREs (pISRE). The ISRE elements in pISRE are from the ISG15 gene, and pISRE was obtained from Dr L. Zhang (University of Nebraska, NE, USA). IRF3 stimulated pISRE promoter activity by more than 50-fold in bovine cells (9.1.3), 40-fold in 293 cells or 15-fold in neuro-2A cells (Fig. 3a and Supplementary Table S2a). Activation of pISRE promoter activity by IRF3 was inhibited by almost threefold in 9.1.3 or neuro-2A cells and sixfold in 293 cells when 1 µg wt bICP0 was used in the transfection. The zinc RING finger mutant (13G/51A) was unable to effectively repress IRF3 induction of pISRE promoter activity in 9.1.3 cells. In 293 or neuro-2A cells, the 13G/51A mutant reduced pISRE promoter activity almost as efficiently as wt bICP0. The C-terminal bICP0 mutant ({Delta}bICP0) and wt bICP0 inhibited IRF3 induction of pISRE promoter activity with similar efficiency, suggesting that aa 1–356 were sufficient for inhibiting pISRE promoter activity.



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Fig. 3. Regulation of ISRE-dependent transcription by bICP0. Neuro-2A, 293 or 9.1.3 cells (1x105 in a 60 mm dish) were transfected with 1 µg pISRE promoter. Cultures were also cotransfected with 2 µg IRF3 (a) or IRF7 (b) and 1, 2 or 3 µg of wt bICP0, 13G/51A mutant or the {Delta}bICP0 mutant. Plasmid DNA was maintained at the same concentration by including a blank expression vector (pcDNA3.1) in the transfection mix. (c) The LR promoter (p0.95cat/1) was cotransfected with 1 or 2 µg wt bICP0 plasmid in 293 cells (empty bars) or 9.1.3 cells (filled bars). CAT activity was measured as described in the legend to Fig. 1. Basal values for the LR promoter or pISRE were normalized to 1 and the values presented are fold activation relative to basal promoter levels. Results are means of four experiments.

 
IRF7 stimulated pISRE promoter activity by more than 15-fold in 9.1.3 cells, 67-fold in 293 cells or fourfold in neuro-2A cells. In 9.1.3 cells, higher concentrations of bICP0 were necessary to inhibit pISRE promoter activity following activation with IRF7 (Fig. 3b and Supplementary Table S2b). At higher concentrations of the 13G/51A plasmid, pISRE promoter activity was repressed in 9.1.3 cells almost as efficiently as by wt bICP0. In 293 cells, 1 µg bICP0 or {Delta}bICP0 inhibited the ability of IRF7 to activate pISRE promoter activity by more than 10-fold. Conversely, the 13G/51A construct repressed IRF7 induction of the pISRE promoter by only three- to fourfold in 293 cells. In neuro-2A cells, bICP0 (wt, the 13G/51A mutant or the {Delta}bICP0 mutant) repressed promoter activity with similar efficiency. As expected, bICP0 activated the LR promoter in 293 or 9.1.3 cells (Fig. 3c and Supplementary Table S2c). These studies suggested that the zinc RING finger was necessary for inhibiting pISRE promoter activity in certain cell types.

Collectively, these studies indicated that bICP0 repressed the IFN-{beta} promoter (an early IFN response) and ISRE-dependent transcription (a relatively late IFN response). Conversely, bICP0 activated the LR promoter in 293, 9.1.3 and neuro-2A cells. These studies do not preclude the possibility that bICP0 inhibits other cellular promoters, nor do they explain how bICP0 inhibited IFN-{beta}- or ISRE-dependent promoter activity. We suggest that, in general, interactions between bICP0 and cellular transcription factors stimulate viral transcription, but repress certain cellular promoters.

The two point mutations within the bICP0 zinc RING finger prevent activation of the thymidine kinase (TK) promoter and productive infection in all cell types that have been examined (Inman et al., 2001). In contrast, the zinc RING finger was only required to inhibit IRF3 induction of pISRE promoter activity in bovine cells (9.1.3) and IKK{varepsilon} induction of IFN-{beta} promoter activity, suggesting that the zinc RING finger was necessary for inhibiting a specific IRF3-dependent step. HSV-1-encoded ICP0 also represses the antiviral effects of IFN (Mossman et al., 2000; Mossman & Smiley, 2002) by inhibiting IRF3 and IRF7 induction of IFN-stimulated genes, and the zinc RING finger is required for blocking activation (Lin et al., 2004).

In all cell types examined, the {Delta}bICP0 deletion mutant efficiently inhibited pISRE and IFN-{beta} promoter activity, suggesting that aa 357–676 were not important. The C terminus of HSV-1 ICP0 also does not play a major role in blocking IFN-dependent transcription (Lin et al., 2004). The {Delta}bICP0 construct does not activate a simple HSV TK promoter (Inman et al., 2001; Zhang & Jones, 2001), suggesting that bICP0 sequences required for activating transcription are distinct from sequences that inhibit IFN-dependent transcription. A recent study has identified several functional domains within bICP0 that are necessary for activating a simple viral promoter (Zhang et al., 2005). It will be of interest to identify the bICP0 functional domains that inhibit IFN-dependent transcription and to compare them with sequences necessary for activating viral transcription.

Although we believe that bICP0 is an important viral gene that inhibits the IFN response, it is likely that other BHV-1 genes antagonize the IFN response following infection. Support for this hypothesis comes from studies demonstrating that HSV-1 genes encoding ICP0, 34·5 and Us11 inhibit the IFN response (Mossman et al., 2000, 2001; Katze et al., 2002; Mossman & Smiley, 2002). BHV-1 apparently does not encode a 34·5 homologue, suggesting that other BHV-1 genes with similar functions exist. Future studies will attempt to identify other viral genes that regulate the IFN response, and elucidate their role in pathogenesis.


   ACKNOWLEDGEMENTS
 
This work was supported by two USDA grants (2002-35204 and 2003-02213) and a Public Health Service grant (1P20RR15635).


   REFERENCES
Top
ABSTRACT
MAIN TEXT
REFERENCES
 
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.[Abstract/Free Full Text]

Attwooll, C., Denchi, E. L. & Helin, K. (2004). The E2F family: specific functions and overlapping interests. EMBO J 23, 4709–4716.[CrossRef][Medline]

Barnes, B., Lubyova, B. & Pitha, P. M. (2002). On the role of IRF in host defense. J Interferon Cytokine Res 22, 59–71.[CrossRef][Medline]

Bratanich, A. C. & Jones, C. J. (1992). Localization of cis-acting sequences in the latency-related promoter of bovine herpesvirus 1 which are regulated by neuronal cell type factors and immediate-early genes. J Virol 66, 6099–6106.[Abstract/Free Full Text]

Chakravarti, D., Ogryzko, V., Kao, H.-Y., Nash, A., Chen, H., Nakatani, Y. & Evans, R. M. (1999). A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity. Cell 96, 393–403.[CrossRef][Medline]

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.[Abstract/Free Full Text]

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.[Medline]

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][Medline]

Everett, R. D. (2000). ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 22, 761–770.[CrossRef][Medline]

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][Medline]

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][Medline]

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][Medline]

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.[Abstract/Free Full Text]

Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M. & Maniatis, T. (2003). IKK{varepsilon} and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4, 491–496.[CrossRef][Medline]

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

Hamamori, Y., Sartorelli, V., Ogryzko, V., Puri, P. L., Wu, H.-Y., Wang, J. Y. J., Nakatani, Y. & Kedes, L. (1999). Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Cell 96, 405–413.[CrossRef][Medline]

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.[Abstract/Free Full Text]

Honda, K., Yanai, H., Negishi, H. & 8 other authors (2005). IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434, 772–777.[CrossRef][Medline]

Inman, M., Zhang, Y., Geiser, V. & Jones, C. (2001). 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.[Abstract/Free Full Text]

Jones, C. (2003). Herpes simplex virus type 1 and bovine herpesvirus 1 latency. Clin Microbiol Rev 16, 79–95.[Abstract/Free Full Text]

Jones, C., Delhon, G., Bratanich, A., Kutish, G. & Rock, D. (1990). Analysis of the transcriptional promoter which regulates the latency-related transcript of bovine herpesvirus 1. J Virol 64, 1164–1170.[Abstract/Free Full Text]

Katze, M. G., He, Y. & Gale, M. (2002). Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2, 675–687.[CrossRef][Medline]

Lin, R., Noyce, R. S., Collins, S. E., Everett, R. D. & Mossman, K. L. (2004). The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J Virol 78, 1675–1684.[Abstract/Free Full Text]

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.[Abstract]

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.[Abstract]

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.[Abstract/Free Full Text]

Mossman, K. L., Saffran, H. A. & Smiley, J. R. (2000). Herpes simplex virus ICP0 mutants are hypersensitive to interferon. J Virol 74, 2052–2056.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

Munshi, N., Agalioti, T., Lomvardas, S., Merika, M., Chen, G. & Thanos, D. (2001). Coordination of a transcriptional switch by HMGI(Y) acetylation. Science 293, 1133–1136.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

Peng, W., Henderson, G., Inman, M., BenMohamed, L., Perng, G.-C., Wechsler, S. L. & Jones, C. (2005). The locus encompassing the latency-associated transcript of herpes simplex virus type 1 interferes with and delays interferon expression in productively infected neuroblastoma cells and trigeminal ganglia of acutely infected mice. J Virol 79, 6162–6171.[Abstract/Free Full Text]

Peters, G. A., Khoo, D., Mohr, I. & Sen, G. C. (2002). Inhibition of PACT-mediated activation of PKR by the herpes simplex virus type 1 Us11 protein. J Virol 76, 11054–11064.[Abstract/Free Full Text]

Sarkar, S. N., Peters, K. L., Elco, C. P., Sakamoto, S., Pal, S. & Sen, G. C. (2004). Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat Struct Mol Biol 11, 1060–1067.[CrossRef][Medline]

Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G.-P., Lin, R. & Hiscott, J. (2003). Triggering the interferon antiviral response through an IKK-related pathway. Science 300, 1148–1151.[Abstract/Free Full Text]

Tikoo, S. K., Campos, M. & Babiuk, L. A. (1995). Bovine herpesvirus 1 (BHV-1): biology, pathogenesis, and control. Adv Virus Res 45, 191–223.[Medline]

Wirth, U. V., Fraefel, C., Vogt, B., Vlcek, C., Paces, 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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

Received 14 April 2005; accepted 21 July 2005.



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