Abstract
To assess the role of the equine herpesvirus type 1 (EHV-1) ICP0 protein (EICP0) in gene regulation, a variety of molecular studies on the EICP0 gene and gene products of both the attenuated cell culture-adapted Kentucky A (KyA) strain and the Ab4p strain were conducted. These investigations revealed that (i) the ICP0 open reading frame (ORF) of the KyA virus strain is 1,257 bp in size and would encode a protein of 419 amino acids, and in comparison to the ICP0 gene (ORF63) of the Ab4p strain of 1,596 bp (E. A. Telford, M. S. Watson, K. McBride, and A. J. Davison, Virology 189:304-316, 1992), it has an internal in-frame deletion of 339 bp; (ii) one early transcript of 1.4 kb predicted to encode the EICP0 protein and a late transcript of 1.8 kb are detected in Northern blot analyses using probes containing the EICP0 ORF; (iii) the KyA EICP0 protein (50 kDa) and the Ab4p EICP0 protein (80 kDa) are expressed as several species of early proteins that are first detected at 3 to 4 h postinfection by Western blot analyses of infected-cell polypeptides, using an antiserum generated to a TrpE fusion protein that harbors amino acids 46 to 153 of the EICP0 protein; and (iv) the EICP0 protein of both EHV-1 strains is a potent transactivator of EHV-1 genes. Transient expression assays using a simian virus 40 expression construct of the EICP0 protein of the KyA strain showed that the EICP0 protein independently transactivated chloramphenicol acetyltransferase reporter constructs under the control of the immediate-early promoter (3.9-fold), the early thymidine kinase promoter (95-fold), the late (gamma1) IR5 promoter (85-fold), and the late (gamma2) glycoprotein K promoter (21-fold). The finding that the EICP0 protein of the KyA virus can function as an activator of gene expression indicates that amino acids corresponding to residues 319 to 431 of the Ab4p EICP0 protein are not essential for EICP0 transactivation of EHV-1 promoters.
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- Allen G. P., Bryans J. T. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections. Prog Vet Microbiol Immunol. 1986;2:78–144. [PubMed] [Google Scholar]
- Baumann R. P., Staczek J., O'Callaghan D. J. Equine herpesvirus type 1 defective-interfering (DI) particle DNA structure: the central region of the inverted repeat is deleted from DI DNA. Virology. 1987 Jul;159(1):137–146. doi: 10.1016/0042-6822(87)90356-4. [DOI] [PubMed] [Google Scholar]
- Baxi M. K., Efstathiou S., Lawrence G., Whalley J. M., Slater J. D., Field H. J. The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons. J Gen Virol. 1995 Dec;76(Pt 12):3113–3118. doi: 10.1099/0022-1317-76-12-3113. [DOI] [PubMed] [Google Scholar]
- Cai W., Schaffer P. A. A cellular function can enhance gene expression and plating efficiency of a mutant defective in the gene for ICP0, a transactivating protein of herpes simplex virus type 1. J Virol. 1991 Aug;65(8):4078–4090. doi: 10.1128/jvi.65.8.4078-4090.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caughman G. B., Staczek J., O'Callaghan D. J. Equine herpesvirus type 1 infected cell polypeptides: evidence for immediate early/early/late regulation of viral gene expression. Virology. 1985 Aug;145(1):49–61. doi: 10.1016/0042-6822(85)90200-4. [DOI] [PubMed] [Google Scholar]
- Chen J. X., Zhu X. X., Silverstein S. Mutational analysis of the sequence encoding ICP0 from herpes simplex virus type 1. Virology. 1991 Jan;180(1):207–220. doi: 10.1016/0042-6822(91)90025-7. [DOI] [PubMed] [Google Scholar]
- Chen M., Harty R. N., Zhao Y., Holden V. R., O'Callaghan D. J. Expression of an equine herpesvirus 1 ICP22/ICP27 hybrid protein encoded by defective interfering particles associated with persistent infection. J Virol. 1996 Jan;70(1):313–320. doi: 10.1128/jvi.70.1.313-320.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheung A. K. Cloning of the latency gene and the early protein 0 gene of pseudorabies virus. J Virol. 1991 Oct;65(10):5260–5271. doi: 10.1128/jvi.65.10.5260-5271.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ciufo D. M., Mullen M. A., Hayward G. S. Identification of a dimerization domain in the C-terminal segment of the IE110 transactivator protein from herpes simplex virus. J Virol. 1994 May;68(5):3267–3282. doi: 10.1128/jvi.68.5.3267-3282.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clements G. B., Stow N. D. A herpes simplex virus type 1 mutant containing a deletion within immediate early gene 1 is latency-competent in mice. J Gen Virol. 1989 Sep;70(Pt 9):2501–2506. doi: 10.1099/0022-1317-70-9-2501. [DOI] [PubMed] [Google Scholar]
- Colle C. F., 3rd, O'Callaghan D. J. Transcriptional analyses of the unique short segment of EHV-1 strain Kentucky A. Virus Genes. 1995 Feb;9(3):257–268. doi: 10.1007/BF01702881. [DOI] [PubMed] [Google Scholar]
- Colle C. F., 3rd, Tarbet E. B., Grafton W. D., Jennings S. R., O'Callaghan D. J. Equine herpesvirus-1 strain KyA, a candidate vaccine strain, reduces viral titers in mice challenged with a pathogenic strain, RacL. Virus Res. 1996 Aug;43(2):111–124. doi: 10.1016/0168-1702(96)01324-x. [DOI] [PubMed] [Google Scholar]
- Crabb B. S., Studdert M. J. Equine herpesviruses 4 (equine rhinopneumonitis virus) and 1 (equine abortion virus). Adv Virus Res. 1995;45:153–190. doi: 10.1016/s0065-3527(08)60060-3. [DOI] [PubMed] [Google Scholar]
- Davido D. J., Leib D. A. Role of cis-acting sequences of the ICPO promoter of herpes simplex virus type 1 in viral pathogenesis, latency and reactivation. J Gen Virol. 1996 Aug;77(Pt 8):1853–1863. doi: 10.1099/0022-1317-77-8-1853. [DOI] [PubMed] [Google Scholar]
- Elliott G., O'Hare P. Equine herpesvirus 1 gene 12, the functional homologue of herpes simplex virus VP16, transactivates via octamer sequences in the equine herpesvirus IE gene promoter. Virology. 1995 Oct 20;213(1):258–262. doi: 10.1006/viro.1995.1568. [DOI] [PubMed] [Google Scholar]
- Everett R. D. A detailed mutational analysis of Vmw110, a trans-acting transcriptional activator encoded by herpes simplex virus type 1. EMBO J. 1987 Jul;6(7):2069–2076. doi: 10.1002/j.1460-2075.1987.tb02472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Everett R. D., Barlow P., Milner A., Luisi B., Orr A., Hope G., Lyon D. A novel arrangement of zinc-binding residues and secondary structure in the C3HC4 motif of an alpha herpes virus protein family. J Mol Biol. 1993 Dec 20;234(4):1038–1047. doi: 10.1006/jmbi.1993.1657. [DOI] [PubMed] [Google Scholar]
- Everett R. D., Orr A., Elliott M. High level expression and purification of herpes simplex virus type 1 immediate early polypeptide Vmw110. Nucleic Acids Res. 1991 Nov 25;19(22):6155–6161. doi: 10.1093/nar/19.22.6155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Everett R., Orr A., Elliott M. The equine herpesvirus 1 gene 63 RING finger protein partially complements Vmw110, its herpes simplex virus type 1 counterpart. J Gen Virol. 1995 Sep;76(Pt 9):2369–2374. doi: 10.1099/0022-1317-76-9-2369. [DOI] [PubMed] [Google Scholar]
- Flowers C. C., O'Callaghan D. J. The equine herpesvirus type 1 (EHV-1) homolog of herpes simplex virus type 1 US9 and the nature of a major deletion within the unique short segment of the EHV-1 KyA strain genome. Virology. 1992 Sep;190(1):307–315. doi: 10.1016/0042-6822(92)91217-i. [DOI] [PubMed] [Google Scholar]
- Fraefel C., Zeng J., Choffat Y., Engels M., Schwyzer M., Ackermann M. Identification and zinc dependence of the bovine herpesvirus 1 transactivator protein BICP0. J Virol. 1994 May;68(5):3154–3162. doi: 10.1128/jvi.68.5.3154-3162.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freemont P. S. The RING finger. A novel protein sequence motif related to the zinc finger. Ann N Y Acad Sci. 1993 Jun 11;684:174–192. doi: 10.1111/j.1749-6632.1993.tb32280.x. [DOI] [PubMed] [Google Scholar]
- Gray W. L., Baumann R. P., Robertson A. T., Caughman G. B., O'Callaghan D. J., Staczek J. Regulation of equine herpesvirus type 1 gene expression: characterization of immediate early, early, and late transcription. Virology. 1987 May;158(1):79–87. doi: 10.1016/0042-6822(87)90240-6. [DOI] [PubMed] [Google Scholar]
- Gray W. L., Baumann R. P., Robertson A. T., O'Callaghan D. J., Staczek J. Characterization and mapping of equine herpesvirus type 1 immediate early, early, and late transcripts. Virus Res. 1987 Sep;8(3):233–244. doi: 10.1016/0168-1702(87)90018-9. [DOI] [PubMed] [Google Scholar]
- Grundy F. J., Baumann R. P., O'Callaghan D. J. DNA sequence and comparative analyses of the equine herpesvirus type 1 immediate early gene. Virology. 1989 Sep;172(1):223–236. doi: 10.1016/0042-6822(89)90124-4. [DOI] [PubMed] [Google Scholar]
- Harty R. N., Holden V. R., O'Callaghan D. J. Transcriptional and translational analyses of the UL2 gene of equine herpesvirus 1: a homolog of UL55 of herpes simplex virus type 1 that is maintained in the genome of defective interfering particles. J Virol. 1993 Apr;67(4):2255–2265. doi: 10.1128/jvi.67.4.2255-2265.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harty R. N., O'Callaghan D. J. An early gene maps within and is 3' coterminal with the immediate-early gene of equine herpesvirus 1. J Virol. 1991 Jul;65(7):3829–3838. doi: 10.1128/jvi.65.7.3829-3838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holden V. R., Yalamanchili R. R., Harty R. N., O'Callaghan D. J. ICP22 homolog of equine herpesvirus 1: expression from early and late promoters. J Virol. 1992 Feb;66(2):664–673. doi: 10.1128/jvi.66.2.664-673.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holden V. R., Zhao Y., Thompson Y., Caughman G. B., Smith R. H., O'Callaghan D. J. Characterization of the regulatory function of the ICP22 protein of equine herpesvirus type 1. Virology. 1995 Jul 10;210(2):273–282. doi: 10.1006/viro.1995.1344. [DOI] [PubMed] [Google Scholar]
- Holden V. R., Zhao Y., Thompson Y., Caughman G. B., Smith R. H., O'Callaghan D. J. Characterization of the regulatory function of the ICP22 protein of equine herpesvirus type 1. Virology. 1995 Jul 10;210(2):273–282. doi: 10.1006/viro.1995.1344. [DOI] [PubMed] [Google Scholar]
- Kim S. K., Holden V. R., O'Callaghan D. J. The ICP22 protein of equine herpesvirus 1 cooperates with the IE protein to regulate viral gene expression. J Virol. 1997 Feb;71(2):1004–1012. doi: 10.1128/jvi.71.2.1004-1012.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim S. K., Smith R. H., O'Callaghan D. J. Characterization of DNA binding properties of the immediate-early gene product of equine herpesvirus type 1. Virology. 1995 Oct 20;213(1):46–56. doi: 10.1006/viro.1995.1545. [DOI] [PubMed] [Google Scholar]
- Koerner T. J., Hill J. E., Myers A. M., Tzagoloff A. High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors. Methods Enzymol. 1991;194:477–490. doi: 10.1016/0076-6879(91)94036-c. [DOI] [PubMed] [Google Scholar]
- Lees-Miller S. P., Long M. C., Kilvert M. A., Lam V., Rice S. A., Spencer C. A. Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0. J Virol. 1996 Nov;70(11):7471–7477. doi: 10.1128/jvi.70.11.7471-7477.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsumura T., O'Callaghan D. J., Kondo T., Kamada M. Lack of virulence of the murine fibroblast adapted strain, Kentucky A (KyA), of equine herpesvirus type 1 (EHV-1) in young horses. Vet Microbiol. 1996 Feb;48(3-4):353–365. doi: 10.1016/0378-1135(09)59999-3. [DOI] [PubMed] [Google Scholar]
- Matsumura T., Smith R. H., O'Callaghan D. J. DNA sequence and transcriptional analyses of the region of the equine herpesvirus type 1 Kentucky A strain genome encoding glycoprotein C. Virology. 1993 Apr;193(2):910–923. doi: 10.1006/viro.1993.1200. [DOI] [PubMed] [Google Scholar]
- Meredith M., Orr A., Elliott M., Everett R. Separation of sequence requirements for HSV-1 Vmw110 multimerisation and interaction with a 135-kDa cellular protein. Virology. 1995 May 10;209(1):174–187. doi: 10.1006/viro.1995.1241. [DOI] [PubMed] [Google Scholar]
- 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]
- Moriuchi H., Moriuchi M., Cohen J. I. The RING finger domain of the varicella-zoster virus open reading frame 61 protein is required for its transregulatory functions. Virology. 1994 Nov 15;205(1):238–246. doi: 10.1006/viro.1994.1639. [DOI] [PubMed] [Google Scholar]
- Moriuchi H., Moriuchi M., Smith H. A., Straus S. E., Cohen J. I. Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0. J Virol. 1992 Dec;66(12):7303–7308. doi: 10.1128/jvi.66.12.7303-7308.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moriuchi H., Moriuchi M., Straus S. E., Cohen J. I. Varicella-zoster virus (VZV) open reading frame 61 protein transactivates VZV gene promoters and enhances the infectivity of VZV DNA. J Virol. 1993 Jul;67(7):4290–4295. doi: 10.1128/jvi.67.7.4290-4295.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nagpal S., Ostrove J. M. Characterization of a potent varicella-zoster virus-encoded trans-repressor. J Virol. 1991 Oct;65(10):5289–5296. doi: 10.1128/jvi.65.10.5289-5296.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Callaghan D. J., Hyde J. M., Gentry G. A., Randall C. C. Kinetics of viral deoxyribonucleic acid, protein, and infectious particle production and alterations in host macromolecular syntheses in equine abortion (herpes) virus-infected cells. J Virol. 1968 Aug;2(8):793–804. doi: 10.1128/jvi.2.8.793-804.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Purewal A. S., Allsopp R., Riggio M., Telford E. A., Azam S., Davison A. J., Edington N. Equid herpesviruses 1 and 4 encode functional homologs of the herpes simplex virus type 1 virion transactivator protein, VP16. Virology. 1994 Jan;198(1):385–389. doi: 10.1006/viro.1994.1047. [DOI] [PubMed] [Google Scholar]
- RANDALL C. C., LAWSON L. A. Adaptation of equine abortion virus to Earle's L cells in serum-free medium with plaque formation. Proc Soc Exp Biol Med. 1962 Jul;110:487–489. doi: 10.3181/00379727-110-27558. [DOI] [PubMed] [Google Scholar]
- Ralph W. M., Jr, Cabatingan M. S., Schaffer P. A. Induction of herpes simplex virus type 1 immediate-early gene expression by a cellular activity expressed in Vero and NB41A3 cells after growth arrest-release. J Virol. 1994 Nov;68(11):6871–6882. doi: 10.1128/jvi.68.11.6871-6882.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sacks W. R., Schaffer P. A. Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture. J Virol. 1987 Mar;61(3):829–839. doi: 10.1128/jvi.61.3.829-839.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saurin A. J., Borden K. L., Boddy M. N., Freemont P. S. Does this have a familiar RING? Trends Biochem Sci. 1996 Jun;21(6):208–214. [PubMed] [Google Scholar]
- Senkevich T. G., Koonin E. V., Buller R. M. A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology. 1994 Jan;198(1):118–128. doi: 10.1006/viro.1994.1014. [DOI] [PubMed] [Google Scholar]
- Smith R. H., Caughman G. B., O'Callaghan D. J. Characterization of the regulatory functions of the equine herpesvirus 1 immediate-early gene product. J Virol. 1992 Feb;66(2):936–945. doi: 10.1128/jvi.66.2.936-945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith R. H., Holden V. R., O'Callaghan D. J. Nuclear localization and transcriptional activation activities of truncated versions of the immediate-early gene product of equine herpesvirus 1. J Virol. 1995 Jun;69(6):3857–3862. doi: 10.1128/jvi.69.6.3857-3862.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith R. H., Zhao Y., O'Callaghan D. J. The equine herpesvirus 1 (EHV-1) UL3 gene, an ICP27 homolog, is necessary for full activation of gene expression directed by an EHV-1 late promoter. J Virol. 1993 Feb;67(2):1105–1109. doi: 10.1128/jvi.67.2.1105-1109.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith R. H., Zhao Y., O'Callaghan D. J. The equine herpesvirus type 1 immediate-early gene product contains an acidic transcriptional activation domain. Virology. 1994 Aug 1;202(2):760–770. doi: 10.1006/viro.1994.1398. [DOI] [PubMed] [Google Scholar]
- Stevenson D., Colman K. L., Davison A. J. Characterization of the varicella-zoster virus gene 61 protein. J Gen Virol. 1992 Mar;73(Pt 3):521–530. doi: 10.1099/0022-1317-73-3-521. [DOI] [PubMed] [Google Scholar]
- Stevenson D., Colman K. L., Davison A. J. Delineation of a sequence required for nuclear localization of the protein encoded by varicella-zoster virus gene 61. J Gen Virol. 1994 Nov;75(Pt 11):3229–3233. doi: 10.1099/0022-1317-75-11-3229. [DOI] [PubMed] [Google Scholar]
- Stow N. D., Stow E. C. 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. 1986 Dec;67(Pt 12):2571–2585. doi: 10.1099/0022-1317-67-12-2571. [DOI] [PubMed] [Google Scholar]
- Telford E. A., Watson M. S., McBride K., Davison A. J. The DNA sequence of equine herpesvirus-1. Virology. 1992 Jul;189(1):304–316. doi: 10.1016/0042-6822(92)90706-u. [DOI] [PubMed] [Google Scholar]
- Watanabe S., Ono E., Shimizu Y., Kida H. Pseudorabies virus early protein 0 transactivates the viral gene promoters. J Gen Virol. 1995 Nov;76(Pt 11):2881–2885. doi: 10.1099/0022-1317-76-11-2881. [DOI] [PubMed] [Google Scholar]
- Wirth U. V., Fraefel C., Vogt B., Vlcek C., Paces V., Schwyzer M. 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. 1992 May;66(5):2763–2772. doi: 10.1128/jvi.66.5.2763-2772.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yalamanchili R. R., O'Callaghan D. J. Sequence and organization of the genomic termini of equine herpesvirus type 1. Virus Res. 1990 Feb;15(2):149–161. doi: 10.1016/0168-1702(90)90005-v. [DOI] [PubMed] [Google Scholar]
- Yalamanchili R. R., Raengsakulrach B., O'Callaghan D. J. Equine herpesvirus 1 sequence near the left terminus codes for two open reading frames. Virus Res. 1991 Mar;18(2-3):109–116. doi: 10.1016/0168-1702(91)90012-k. [DOI] [PubMed] [Google Scholar]
- Yao F., Schaffer P. A. 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. 1995 Oct;69(10):6249–6258. doi: 10.1128/jvi.69.10.6249-6258.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yao F., Schaffer P. A. Physical interaction between the herpes simplex virus type 1 immediate-early regulatory proteins ICP0 and ICP4. J Virol. 1994 Dec;68(12):8158–8168. doi: 10.1128/jvi.68.12.8158-8168.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhao Y., Holden V. R., Harty R. N., O'Callaghan D. J. Identification and transcriptional analyses of the UL3 and UL4 genes of equine herpesvirus 1, homologs of the ICP27 and glycoprotein K genes of herpes simplex virus. J Virol. 1992 Sep;66(9):5363–5372. doi: 10.1128/jvi.66.9.5363-5372.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhao Y., Holden V. R., Smith R. H., O'Callaghan D. J. Regulatory function of the equine herpesvirus 1 ICP27 gene product. J Virol. 1995 May;69(5):2786–2793. doi: 10.1128/jvi.69.5.2786-2793.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]