Abstract
The infection of vaccinia virus in Chinese hamster ovary (CHO) cells produces a rapid shutdown in protein synthesis, and the infection is abortive (R.R. Drillien, D. Spehner, and A. Kirn, Virology 111:488-499, 1978; D.E. Hruby, D.L. Lynn, R. Condit, and J.R. Kates, J. Gen. Virol. 47:485-488, 1980). Cowpox virus, which can productively infect CHO cells, had previously been shown to contain a host range gene, CHOhr, which confers on vaccinia virus the ability to replicate in CHO cells (D. Spehner, S. Gillard, R. Drillien, and A. Kirn, J. Virol. 62:1297-1304, 1988). We found that CHO cells underwent apoptosis when infected with vaccinia virus. The expression of the CHOhr gene in vaccinia virus allowed for the expression of late virus genes. CHOhr also delayed or prevented vaccinia virus-induced apoptosis in CHO cells such that there was sufficient time for replication of the virus before the cell died. The E1B 19K gene from adenovirus also delayed vaccinia virus-induced apoptosis; however, there was no detectable expression of late virus genes. Furthermore, E1B 19K also delayed cell death in CHO cells which had been productively infected with vaccinia virus. This study identifies a new antiapoptotic gene from cowpox virus, CHOhr, for which the protein contains an ankyrin-like repeat and shows no significant homology to other proteins. This work also indicates that an antiapoptotic gene from one virus family can delay cell death in an infection of a virus from a different family.
Full Text
The Full Text of this article is available as a PDF (403.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
- Bennett V. Ankyrins. Adaptors between diverse plasma membrane proteins and the cytoplasm. J Biol Chem. 1992 May 5;267(13):8703–8706. [PubMed] [Google Scholar]
- Birnbaum M. J., Clem R. J., Miller L. K. An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol. 1994 Apr;68(4):2521–2528. doi: 10.1128/jvi.68.4.2521-2528.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bork P. Hundreds of ankyrin-like repeats in functionally diverse proteins: mobile modules that cross phyla horizontally? Proteins. 1993 Dec;17(4):363–374. doi: 10.1002/prot.340170405. [DOI] [PubMed] [Google Scholar]
- Buller R. M., Palumbo G. J. Poxvirus pathogenesis. Microbiol Rev. 1991 Mar;55(1):80–122. doi: 10.1128/mr.55.1.80-122.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bursch W., Kleine L., Tenniswood M. The biochemistry of cell death by apoptosis. Biochem Cell Biol. 1990 Sep;68(9):1071–1074. doi: 10.1139/o90-160. [DOI] [PubMed] [Google Scholar]
- Chang H. W., Watson J. C., Jacobs B. L. The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4825–4829. doi: 10.1073/pnas.89.11.4825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
- Clem R. J., Fechheimer M., Miller L. K. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388–1390. doi: 10.1126/science.1962198. [DOI] [PubMed] [Google Scholar]
- Clouston W. M., Kerr J. F. Apoptosis, lymphocytotoxicity and the containment of viral infections. Med Hypotheses. 1985 Dec;18(4):399–404. doi: 10.1016/0306-9877(85)90107-0. [DOI] [PubMed] [Google Scholar]
- Crook N. E., Clem R. J., Miller L. K. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol. 1993 Apr;67(4):2168–2174. doi: 10.1128/jvi.67.4.2168-2174.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davies M. V., Chang H. W., Jacobs B. L., Kaufman R. J. The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms. J Virol. 1993 Mar;67(3):1688–1692. doi: 10.1128/jvi.67.3.1688-1692.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis L. H., Bennett V. Mapping the binding sites of human erythrocyte ankyrin for the anion exchanger and spectrin. J Biol Chem. 1990 Jun 25;265(18):10589–10596. [PubMed] [Google Scholar]
- Drillien R., Koehren F., Kirn A. Host range deletion mutant of vaccinia virus defective in human cells. Virology. 1981 Jun;111(2):488–499. doi: 10.1016/0042-6822(81)90351-2. [DOI] [PubMed] [Google Scholar]
- Drillien R., Spehner D., Kirn A. Host range restriction of vaccinia virus in Chinese hamster ovary cells: relationship to shutoff of protein synthesis. J Virol. 1978 Dec;28(3):843–850. doi: 10.1128/jvi.28.3.843-850.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gagliardini V., Fernandez P. A., Lee R. K., Drexler H. C., Rotello R. J., Fishman M. C., Yuan J. Prevention of vertebrate neuronal death by the crmA gene. Science. 1994 Feb 11;263(5148):826–828. doi: 10.1126/science.8303301. [DOI] [PubMed] [Google Scholar]
- Gillard S., Spehner D., Drillien R., Kirn A. Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5573–5577. doi: 10.1073/pnas.83.15.5573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillard S., Spehner D., Drillien R. Mapping of a vaccinia host range sequence by insertion into the viral thymidine kinase gene. J Virol. 1985 Jan;53(1):316–318. doi: 10.1128/jvi.53.1.316-318.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goebel S. J., Johnson G. P., Perkus M. E., Davis S. W., Winslow J. P., Paoletti E. The complete DNA sequence of vaccinia virus. Virology. 1990 Nov;179(1):247-66, 517-63. doi: 10.1016/0042-6822(90)90294-2. [DOI] [PubMed] [Google Scholar]
- Gooding L. R., Aquino L., Duerksen-Hughes P. J., Day D., Horton T. M., Yei S. P., Wold W. S. The E1B 19,000-molecular-weight protein of group C adenoviruses prevents tumor necrosis factor cytolysis of human cells but not of mouse cells. J Virol. 1991 Jun;65(6):3083–3094. doi: 10.1128/jvi.65.6.3083-3094.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gregory C. D., Dive C., Henderson S., Smith C. A., Williams G. T., Gordon J., Rickinson A. B. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature. 1991 Feb 14;349(6310):612–614. doi: 10.1038/349612a0. [DOI] [PubMed] [Google Scholar]
- Hashimoto S., Ishii A., Yonehara S. The E1b oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int Immunol. 1991 Apr;3(4):343–351. doi: 10.1093/intimm/3.4.343. [DOI] [PubMed] [Google Scholar]
- Henderson S., Huen D., Rowe M., Dawson C., Johnson G., Rickinson A. Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479–8483. doi: 10.1073/pnas.90.18.8479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hershberger P. A., Dickson J. A., Friesen P. D. Site-specific mutagenesis of the 35-kilodalton protein gene encoded by Autographa californica nuclear polyhedrosis virus: cell line-specific effects on virus replication. J Virol. 1992 Sep;66(9):5525–5533. doi: 10.1128/jvi.66.9.5525-5533.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
- Hruby D. E., Lynn D. L., Condit R. C., Kates J. R. Cellular differences in the molecular mechanisms of vaccinia virus host range restriction. J Gen Virol. 1980 Apr;47(2):485–488. doi: 10.1099/0022-1317-47-2-485. [DOI] [PubMed] [Google Scholar]
- Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laherty C. D., Hu H. M., Opipari A. W., Wang F., Dixit V. M. The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B. J Biol Chem. 1992 Dec 5;267(34):24157–24160. [PubMed] [Google Scholar]
- Lambert S., Yu H., Prchal J. T., Lawler J., Ruff P., Speicher D., Cheung M. C., Kan Y. W., Palek J. cDNA sequence for human erythrocyte ankyrin. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1730–1734. doi: 10.1073/pnas.87.5.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee M. A., Yates J. L. BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro. J Virol. 1992 Apr;66(4):1899–1906. doi: 10.1128/jvi.66.4.1899-1906.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee S. B., Esteban M. The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology. 1994 Mar;199(2):491–496. doi: 10.1006/viro.1994.1151. [DOI] [PubMed] [Google Scholar]
- Lux S. E., John K. M., Bennett V. Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. Nature. 1990 Mar 1;344(6261):36–42. doi: 10.1038/344036a0. [DOI] [PubMed] [Google Scholar]
- Marchini A., Tomkinson B., Cohen J. I., Kieff E. BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication. J Virol. 1991 Nov;65(11):5991–6000. doi: 10.1128/jvi.65.11.5991-6000.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin J. M., Veis D., Korsmeyer S. J., Sugden B. Latent membrane protein of Epstein-Barr virus induces cellular phenotypes independently of expression of Bcl-2. J Virol. 1993 Sep;67(9):5269–5278. doi: 10.1128/jvi.67.9.5269-5278.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miura M., Zhu H., Rotello R., Hartwieg E. A., Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993 Nov 19;75(4):653–660. doi: 10.1016/0092-8674(93)90486-a. [DOI] [PubMed] [Google Scholar]
- Oguiura N., Spehner D., Drillien R. Detection of a protein encoded by the vaccinia virus C7L open reading frame and study of its effect on virus multiplication in different cell lines. J Gen Virol. 1993 Jul;74(Pt 7):1409–1413. doi: 10.1099/0022-1317-74-7-1409. [DOI] [PubMed] [Google Scholar]
- Perkus M. E., Goebel S. J., Davis S. W., Johnson G. P., Limbach K., Norton E. K., Paoletti E. Vaccinia virus host range genes. Virology. 1990 Nov;179(1):276–286. doi: 10.1016/0042-6822(90)90296-4. [DOI] [PubMed] [Google Scholar]
- Pickup D. J., Ink B. S., Hu W., Ray C. A., Joklik W. K. Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7698–7702. doi: 10.1073/pnas.83.20.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pickup D. J., Ink B. S., Parsons B. L., Hu W., Joklik W. K. Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6817–6821. doi: 10.1073/pnas.81.21.6817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilder S., Logan J., Shenk T. Deletion of the gene encoding the adenovirus 5 early region 1b 21,000-molecular-weight polypeptide leads to degradation of viral and host cell DNA. J Virol. 1984 Nov;52(2):664–671. doi: 10.1128/jvi.52.2.664-671.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992 May 15;69(4):597–604. doi: 10.1016/0092-8674(92)90223-y. [DOI] [PubMed] [Google Scholar]
- Shchelkunov S. N., Blinov V. M., Sandakhchiev L. S. Ankyrin-like proteins of variola and vaccinia viruses. FEBS Lett. 1993 Mar 15;319(1-2):163–165. doi: 10.1016/0014-5793(93)80059-4. [DOI] [PubMed] [Google Scholar]
- Spehner D., Gillard S., Drillien R., Kirn A. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. J Virol. 1988 Apr;62(4):1297–1304. doi: 10.1128/jvi.62.4.1297-1304.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson J. C., Chang H. W., Jacobs B. L. Characterization of a vaccinia virus-encoded double-stranded RNA-binding protein that may be involved in inhibition of the double-stranded RNA-dependent protein kinase. Virology. 1991 Nov;185(1):206–216. doi: 10.1016/0042-6822(91)90768-7. [DOI] [PubMed] [Google Scholar]
- White E., Grodzicker T., Stillman B. W. Mutations in the gene encoding the adenovirus early region 1B 19,000-molecular-weight tumor antigen cause the degradation of chromosomal DNA. J Virol. 1984 Nov;52(2):410–419. doi: 10.1128/jvi.52.2.410-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White E., Sabbatini P., Debbas M., Wold W. S., Kusher D. I., Gooding L. R. The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol. 1992 Jun;12(6):2570–2580. doi: 10.1128/mcb.12.6.2570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wyllie A. H. Apoptosis: cell death under homeostatic control. Arch Toxicol Suppl. 1987;11:3–10. doi: 10.1007/978-3-642-72558-6_1. [DOI] [PubMed] [Google Scholar]
- Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
- Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]