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. 1991 Jun;65(6):3029–3043. doi: 10.1128/jvi.65.6.3029-3043.1991

Host range specificity of polyomavirus EC mutants in mouse embryonal carcinoma and embryonal stem cells and preimplantation embryos.

F Mélin 1, R Kemler 1, C Kress 1, H Pinon 1, D Blangy 1
PMCID: PMC240958  PMID: 1851869

Abstract

New polyomavirus mutants (PyEC-C) selected on LT1 cells and exhibiting a strong cytopathic effect in all embryonal carcinoma (EC) cell lines tested have been isolated. They were derived by a sequence duplication event from a new multiadapted mutant isolated in PCC4 cells. A quantitative analysis of viral DNA replication and transcription in 3T6 and EC cell lines was performed to compare PyEC-C mutants and PyEC mutants previously isolated on F9 or PCC4 cell lines. Analysis of the results indicated that PyEC-C mutants were more efficient in all EC cell lines tested than all other PyEC mutants; on the contrary, they were less adapted to 3T6 cells than wild-type polyomavirus. In both 3T6 and EC cells, uncoupling between early transcription and viral DNA replication was observed; different viruses were shown to replicate with the same efficiency, while their levels of early transcripts differed by two orders of magnitude. Attempts to correlate the genome structure of the mutants with their biological properties indicate that duplication of protein-binding sequences is not the only event responsible for their phenotype. PyEC mutants were also analyzed with respect to their interactions with early mouse embryos and embryonal stem (ES) cell lines derived from the inner cell mass of blastocysts. They showed different degrees of expression in ES cells and preimplantation embryos. ES cells were most efficiently infected and lysed by mutants which exhibit both a multiadapted and a lytic phenotype in EC cells. Preimplantation embryos were not permissive to any PyEC mutants. However, EC-multiadapted mutants were infectious in blastocysts after two days of in vitro culture.

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Selected References

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

  1. Dandolo L., Aghion J., Blangy D. T-antigen-independent replication of polyomavirus DNA in murine embryonal carcinoma cells. Mol Cell Biol. 1984 Feb;4(2):317–323. doi: 10.1128/mcb.4.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dandolo L., Blangy D., Kamen R. Regulation of polyoma virus transcription in murine embryonal carcinoma cells. J Virol. 1983 Jul;47(1):55–64. doi: 10.1128/jvi.47.1.55-64.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  4. Doetschman T. C., Eistetter H., Katz M., Schmidt W., Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed] [Google Scholar]
  5. Evans M. J., Kaufman M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981 Jul 9;292(5819):154–156. doi: 10.1038/292154a0. [DOI] [PubMed] [Google Scholar]
  6. Foster R., Olsson P. E., Gedamu L. Calcium phosphate-mediated transfection alters metallothionein gene expression in response to Cd2+ and Zn2+. Mol Cell Biol. 1989 Sep;9(9):4105–4108. doi: 10.1128/mcb.9.9.4105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fujimura F. K., Linney E. Polyoma mutants that productively infect F9 embryonal carcinoma cells do not rescue wild-type polyoma in F9 cells. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1479–1483. doi: 10.1073/pnas.79.5.1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Georges E., Vasseur M., Blangy D. Polyoma virus mutants as probes of variety among mouse embryonal carcinoma cell lines. Differentiation. 1982;22(1):62–65. doi: 10.1111/j.1432-0436.1982.tb01225.x. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  10. Gossler A., Doetschman T., Korn R., Serfling E., Kemler R. Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9065–9069. doi: 10.1073/pnas.83.23.9065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  12. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  13. Jakob H., Boon T., Gaillard J., Nicolas J., Jacob F. Tératocarcinome de la spuris: isolement, culture et propriétés de cellules a potentialités multiples. Ann Microbiol (Paris) 1973 Oct;124(3):269–282. [PubMed] [Google Scholar]
  14. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  15. Katinka M., Vasseur M., Montreau N., Yaniv M., Blangy D. Polyoma DNA sequences involved in control of viral gene expression in murine embryonal carcinoma cells. Nature. 1981 Apr 23;290(5808):720–722. doi: 10.1038/290720a0. [DOI] [PubMed] [Google Scholar]
  16. Kemler R., Brûlet P., Schnebelen M. T., Gaillard J., Jacob F. Reactivity of monoclonal antibodies against intermediate filament proteins during embryonic development. J Embryol Exp Morphol. 1981 Aug;64:45–60. [PubMed] [Google Scholar]
  17. Kovesdi I., Satake M., Furukawa K., Reichel R., Ito Y., Nevins J. R. A factor discriminating between the wild-type and a mutant polyomavirus enhancer. Nature. 1987 Jul 2;328(6125):87–89. doi: 10.1038/328087a0. [DOI] [PubMed] [Google Scholar]
  18. Kryszke M. H., Piette J., Yaniv M. Induction of a factor that binds to the polyoma virus A enhancer on differentiation of embryonal carcinoma cells. Nature. 1987 Jul 16;328(6127):254–256. doi: 10.1038/328254a0. [DOI] [PubMed] [Google Scholar]
  19. MacDonald R. J., Swift G. H., Przybyla A. E., Chirgwin J. M. Isolation of RNA using guanidinium salts. Methods Enzymol. 1987;152:219–227. doi: 10.1016/0076-6879(87)52023-7. [DOI] [PubMed] [Google Scholar]
  20. Magnusson G., Nilsson M. G. Viable polyoma virus variant with two origins of DNA replication. Virology. 1982 May;119(1):12–21. doi: 10.1016/0042-6822(82)90060-5. [DOI] [PubMed] [Google Scholar]
  21. Martin G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634–7638. doi: 10.1073/pnas.78.12.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martin M. E., Piette J., Yaniv M., Tang W. J., Folk W. R. Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5839–5843. doi: 10.1073/pnas.85.16.5839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Martínez-Salas E., Linney E., Hassell J., DePamphilis M. L. The need for enhancers in gene expression first appears during mouse development with formation of the zygotic nucleus. Genes Dev. 1989 Oct;3(10):1493–1506. doi: 10.1101/gad.3.10.1493. [DOI] [PubMed] [Google Scholar]
  24. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  25. Melin F., Pinon H., Kress C., Blangy D. Isolation of polyomavirus mutants multiadapted to murine embryonal carcinoma cells. J Virol. 1985 Mar;53(3):862–866. doi: 10.1128/jvi.53.3.862-866.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Melin F., Pinon H., Reiss C., Kress C., Montreau N., Blangy D. Common features of polyomavirus mutants selected on PCC4 embryonal carcinoma cells. EMBO J. 1985 Jul;4(7):1799–1803. doi: 10.1002/j.1460-2075.1985.tb03853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Minty A. J., Caravatti M., Robert B., Cohen A., Daubas P., Weydert A., Gros F., Buckingham M. E. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed] [Google Scholar]
  28. Nicolas J. F., Avner P., Gaillard J., Guenet J. L., Jakob H., Jacob F. Cell lines derived from teratocarcinomas. Cancer Res. 1976 Nov;36(11 Pt 2):4224–4231. [PubMed] [Google Scholar]
  29. Petzoldt U. Regulation of stage-specific gene expression during early mouse development: effect of cytochalasin B and aphidicolin on stage-specific protein synthesis in mouse eggs. Cell Differ. 1984 Dec;15(2-4):163–167. doi: 10.1016/0045-6039(84)90069-1. [DOI] [PubMed] [Google Scholar]
  30. Piette J., Yaniv M. Two different factors bind to the alpha-domain of the polyoma virus enhancer, one of which also interacts with the SV40 and c-fos enhancers. EMBO J. 1987 May;6(5):1331–1337. doi: 10.1002/j.1460-2075.1987.tb02372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pine R., Levy D. E., Reich N., Darnell J. E., Jr Transcriptional stimulation by CaPO4-DNA precipitates. Nucleic Acids Res. 1988 Feb 25;16(4):1371–1378. doi: 10.1093/nar/16.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Smith A. G., Hooper M. L. Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells. Dev Biol. 1987 May;121(1):1–9. doi: 10.1016/0012-1606(87)90132-1. [DOI] [PubMed] [Google Scholar]
  33. Stevens L. C., Varnum D. S. The development of teratomas from parthenogenetically activated ovarian mouse eggs. Dev Biol. 1974 Apr;37(2):369–380. doi: 10.1016/0012-1606(74)90155-9. [DOI] [PubMed] [Google Scholar]
  34. Stuart G. W., Searle P. F., Chen H. Y., Brinster R. L., Palmiter R. D. A 12-base-pair DNA motif that is repeated several times in metallothionein gene promoters confers metal regulation to a heterologous gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7318–7322. doi: 10.1073/pnas.81.23.7318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tanaka K., Chowdhury K., Chang K. S., Israel M., Ito Y. Isolation and characterization of polyoma virus mutants which grow in murine embryonal carcinoma and trophoblast cells. EMBO J. 1982;1(12):1521–1527. doi: 10.1002/j.1460-2075.1982.tb01349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tyndall C., La Mantia G., Thacker C. M., Favaloro J., Kamen R. A region of the polyoma virus genome between the replication origin and late protein coding sequences is required in cis for both early gene expression and viral DNA replication. Nucleic Acids Res. 1981 Dec 11;9(23):6231–6250. doi: 10.1093/nar/9.23.6231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Vasseur M., Katinka M., Herbomel P., Yaniv M., Blangy D. Physical and biological features of polyoma virus mutants able to infect embryonal carcinoma cell lines. J Virol. 1982 Sep;43(3):800–808. doi: 10.1128/jvi.43.3.800-808.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wasylyk B., Imler J. L., Chatton B., Schatz C., Wasylyk C. Negative and positive factors determine the activity of the polyoma virus enhancer alpha domain in undifferentiated and differentiated cell types. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7952–7956. doi: 10.1073/pnas.85.21.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wasylyk B., Wasylyk C., Flores P., Begue A., Leprince D., Stehelin D. The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. Nature. 1990 Jul 12;346(6280):191–193. doi: 10.1038/346191a0. [DOI] [PubMed] [Google Scholar]
  40. Wasylyk C., Flores P., Gutman A., Wasylyk B. PEA3 is a nuclear target for transcription activation by non-nuclear oncogenes. EMBO J. 1989 Nov;8(11):3371–3378. doi: 10.1002/j.1460-2075.1989.tb08500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]
  42. Wirak D. O., Chalifour L. E., Wassarman P. M., Muller W. J., Hassell J. A., DePamphilis M. L. Sequence-dependent DNA replication in preimplantation mouse embryos. Mol Cell Biol. 1985 Nov;5(11):2924–2935. doi: 10.1128/mcb.5.11.2924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Xiao J. H., Davidson I., Ferrandon D., Rosales R., Vigneron M., Macchi M., Ruffenach F., Chambon P. One cell-specific and three ubiquitous nuclear proteins bind in vitro to overlapping motifs in the domain B1 of the SV40 enhancer. EMBO J. 1987 Oct;6(10):3005–3013. doi: 10.1002/j.1460-2075.1987.tb02606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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