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. 1991 May 1;88(9):3817–3821. doi: 10.1073/pnas.88.9.3817

Constitutive and trophoblast-specific expression of a class of bovine interferon genes.

J C Cross 1, R M Roberts 1
PMCID: PMC51544  PMID: 1708888

Abstract

The early conceptus in sheep and cattle secretes a low molecular weight protein called ovine and bovine trophoblast protein 1 (TP-1) that is critical for establishment of pregnancy. TP-1 is a type I interferon (IFN) and is most related to IFN-omega. Here we have determined if TP-1 genes are regulated similarly to other type I IFNs. Single day 18 bovine conceptuses secrete approximately 10(5) units of IFN antiviral activity per hour in culture, amounts approximately 300 times higher than those produced by Sendai virus-induced leukocytes. Although conceptuses express mRNA for IFN-alpha, IFN-omega, and TP-1, TP-1 constitutes greater than 99% of the IFN produced. In contrast, leukocytes produced predominantly IFN-alpha, although TP-1 mRNA is inducible by Sendai virus to very low levels. TP-1 mRNA is detectable by Northern analysis in conceptuses from early pregnancy but is absent in late gestation placenta and several adult tissues. Transfected bovine TP-1 genes are expressed in human choriocarcinoma (JAR) cells in the absence of any specific stimulus, whereas these cells do not secrete antiviral activity constitutively or after transfection with a bovine IFN-omega gene. The transfected TP-1 gene is not expressed in nontrophoblast cells (mouse L929 and hamster Chinese hamster ovary), however. The 5' promoter region of the TP-1 gene is sufficient to direct trophoblast-specific expression onto a human growth hormone reporter gene in JAR cells. Deletion of the promoter from -450 to -126 results in a 4- to 5-fold decrease in expression. Together these data demonstrate that the genes for TP-1 are inducible by virus but are expressed preferentially in trophoblast cells and are functionally distinct from IFN-omega genes.

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Selected References

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  1. Aboagye-Mathiesen G., Tóth F. D., Juhl C., Nørskov-Lauritsen N., Petersen P. M., Ebbesen P. Purification and initial characterization of human placental trophoblast interferon induced by polyriboinosinic.polyribocytidylic acid. J Gen Virol. 1990 Dec;71(Pt 12):3061–3066. doi: 10.1099/0022-1317-71-12-3061. [DOI] [PubMed] [Google Scholar]
  2. Adolf G. R., Maurer-Fogy I., Kalsner I., Cantell K. Purification and characterization of natural human interferon omega 1. Two alternative cleavage sites for the signal peptidase. J Biol Chem. 1990 Jun 5;265(16):9290–9295. [PubMed] [Google Scholar]
  3. Adolf G. R. Monoclonal antibodies and enzyme immunoassays specific for human interferon (IFN) omega 1: evidence that IFN-omega 1 is a component of human leukocyte IFN. Virology. 1990 Apr;175(2):410–417. doi: 10.1016/0042-6822(90)90425-q. [DOI] [PubMed] [Google Scholar]
  4. Bartol F. F., Roberts R. M., Bazer F. W., Lewis G. S., Godkin J. D., Thatcher W. W. Characterization of proteins produced in vitro by periattachment bovine conceptuses. Biol Reprod. 1985 Apr;32(3):681–693. doi: 10.1095/biolreprod32.3.681. [DOI] [PubMed] [Google Scholar]
  5. Bazer F. W., Vallet J. L., Roberts R. M., Sharp D. C., Thatcher W. W. Role of conceptus secretory products in establishment of pregnancy. J Reprod Fertil. 1986 Mar;76(2):841–850. doi: 10.1530/jrf.0.0760841. [DOI] [PubMed] [Google Scholar]
  6. Capon D. J., Shepard H. M., Goeddel D. V. Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides. Mol Cell Biol. 1985 Apr;5(4):768–779. doi: 10.1128/mcb.5.4.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Cross J. C., Farin C. E., Sharif S. F., Roberts R. M. Characterization of the antiviral activity constitutively produced by murine conceptuses: absence of placental mRNAs for interferon alpha and beta. Mol Reprod Dev. 1990 Jun;26(2):122–128. doi: 10.1002/mrd.1080260205. [DOI] [PubMed] [Google Scholar]
  9. Cross J. C., Roberts R. M. Porcine conceptuses secrete an interferon during the preattachment period of early pregnancy. Biol Reprod. 1989 May;40(5):1109–1118. doi: 10.1095/biolreprod40.5.1109. [DOI] [PubMed] [Google Scholar]
  10. Duc-Goiran P., Chany C., Doly J. Unusually large interferon-alpha-like mRNAs and high expression of interleukin-6 in human fetal annexes. J Biol Chem. 1989 Oct 5;264(28):16507–16511. [PubMed] [Google Scholar]
  11. Duc-Goiran P., Robert-Galliot B., Lopez J., Chany C. Unusual apparently constitutive interferons and antagonists in human placental blood. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5010–5014. doi: 10.1073/pnas.82.15.5010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Farin C. E., Imakawa K., Hansen T. R., McDonnell J. J., Murphy C. N., Farin P. W., Roberts R. M. Expression of trophoblastic interferon genes in sheep and cattle. Biol Reprod. 1990 Aug;43(2):210–218. doi: 10.1095/biolreprod43.2.210. [DOI] [PubMed] [Google Scholar]
  13. Farin C. E., Imakawa K., Roberts R. M. In situ localization of mRNA for the interferon, ovine trophoblast protein-1, during early embryonic development of the sheep. Mol Endocrinol. 1989 Jul;3(7):1099–1107. doi: 10.1210/mend-3-7-1099. [DOI] [PubMed] [Google Scholar]
  14. Fowler A. K., Reed C. D., Giron D. J. Identification of an interferon in murine placentas. Nature. 1980 Jul 17;286(5770):266–267. doi: 10.1038/286266a0. [DOI] [PubMed] [Google Scholar]
  15. Fujita T., Kimura Y., Miyamoto M., Barsoumian E. L., Taniguchi T. Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature. 1989 Jan 19;337(6204):270–272. doi: 10.1038/337270a0. [DOI] [PubMed] [Google Scholar]
  16. Godkin J. D., Bazer F. W., Moffatt J., Sessions F., Roberts R. M. Purification and properties of a major, low molecular weight protein released by the trophoblast of sheep blastocysts at day 13-21. J Reprod Fertil. 1982 May;65(1):141–150. doi: 10.1530/jrf.0.0650141. [DOI] [PubMed] [Google Scholar]
  17. Goeddel D. V., Yelverton E., Ullrich A., Heyneker H. L., Miozzari G., Holmes W., Seeburg P. H., Dull T., May L., Stebbing N. Human leukocyte interferon produced by E. coli is biologically active. Nature. 1980 Oct 2;287(5781):411–416. doi: 10.1038/287411a0. [DOI] [PubMed] [Google Scholar]
  18. Greene J. J., Dyer R. H., Yang L. C., Ts'o P. O. Developmentally regulated expression of the interferon system during Syrian hamster embryogenesis. J Interferon Res. 1984 Fall;4(4):517–527. doi: 10.1089/jir.1984.4.517. [DOI] [PubMed] [Google Scholar]
  19. Hansen T. R., Imakawa K., Polites H. G., Marotti K. R., Anthony R. V., Roberts R. M. Interferon RNA of embryonic origin is expressed transiently during early pregnancy in the ewe. J Biol Chem. 1988 Sep 15;263(26):12801–12804. [PubMed] [Google Scholar]
  20. Hansen T. R., Leaman D. W., Cross J. C., Mathialagan N., Bixby J. A., Roberts R. M. The genes for the trophoblast interferons and the related interferon-alpha II possess distinct 5'-promoter and 3'-flanking sequences. J Biol Chem. 1991 Feb 15;266(5):3060–3067. [PubMed] [Google Scholar]
  21. Hauptmann R., Swetly P. A novel class of human type I interferons. Nucleic Acids Res. 1985 Jul 11;13(13):4739–4749. doi: 10.1093/nar/13.13.4739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Himmler A., Hauptmann R., Adolf G. R., Swetly P. Structure and expression in Escherichia coli of canine interferon-alpha genes. J Interferon Res. 1987 Apr;7(2):173–183. doi: 10.1089/jir.1987.7.173. [DOI] [PubMed] [Google Scholar]
  23. Hiscott J., Cantell K., Weissmann C. Differential expression of human interferon genes. Nucleic Acids Res. 1984 May 11;12(9):3727–3746. doi: 10.1093/nar/12.9.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Imakawa K., Hansen T. R., Malathy P. V., Anthony R. V., Polites H. G., Marotti K. R., Roberts R. M. Molecular cloning and characterization of complementary deoxyribonucleic acids corresponding to bovine trophoblast protein-1: a comparison with ovine trophoblast protein-1 and bovine interferon-alpha II. Mol Endocrinol. 1989 Jan;3(1):127–139. doi: 10.1210/mend-3-1-127. [DOI] [PubMed] [Google Scholar]
  25. Jacobsen K. L., Rockwood G. A., Abolhassani M., Evans D. L., Chitwood S. W., Charamella L. Kinetics of large-scale production of bovine leukocyte interferon, using three viral inducers. Am J Vet Res. 1988 Sep;49(9):1441–1446. [PubMed] [Google Scholar]
  26. Kandefer-Szerszeń M., Szuster A., Rzeski W., Kamińska T., Kawecki Z. The production of bovine interferon in foetal and adult organ cultures and in leukocytes. Arch Immunol Ther Exp (Warsz) 1988;36(4):447–452. [PubMed] [Google Scholar]
  27. Khan N. U., Pulford K. A., Farquharson M. A., Howatson A., Stewart C., Jackson R., McNicol A. M., Foulis A. K. The distribution of immunoreactive interferon-alpha in normal human tissues. Immunology. 1989 Feb;66(2):201–206. [PMC free article] [PubMed] [Google Scholar]
  28. Klemann S. W., Li J. Z., Imakawa K., Cross J. C., Francis H., Roberts R. M. The production, purification, and bioactivity of recombinant bovine trophoblast protein-1 (bovine trophoblast interferon). Mol Endocrinol. 1990 Oct;4(10):1506–1514. doi: 10.1210/mend-4-10-1506. [DOI] [PubMed] [Google Scholar]
  29. Leblanc J. F., Cohen L., Rodrigues M., Hiscott J. Synergism between distinct enhanson domains in viral induction of the human beta interferon gene. Mol Cell Biol. 1990 Aug;10(8):3987–3993. doi: 10.1128/mcb.10.8.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lenardo M. J., Fan C. M., Maniatis T., Baltimore D. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell. 1989 Apr 21;57(2):287–294. doi: 10.1016/0092-8674(89)90966-5. [DOI] [PubMed] [Google Scholar]
  31. MacDonald N. J., Kuhl D., Maguire D., Näf D., Gallant P., Goswamy A., Hug H., Büeler H., Chaturvedi M., de la Fuente J. Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes. Cell. 1990 Mar 9;60(5):767–779. doi: 10.1016/0092-8674(90)90091-r. [DOI] [PubMed] [Google Scholar]
  32. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  33. Moore R. N., Larsen H. S., Horohov D. W., Rouse B. T. Endogenous regulation of macrophage proliferative expansion by colony-stimulating factor-induced interferon. Science. 1984 Jan 13;223(4632):178–181. doi: 10.1126/science.6606850. [DOI] [PubMed] [Google Scholar]
  34. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  35. Pine R., Decker T., Kessler D. S., Levy D. E., Darnell J. E., Jr Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either. Mol Cell Biol. 1990 Jun;10(6):2448–2457. doi: 10.1128/mcb.10.6.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pollard J. W., Bartocci A., Arceci R., Orlofsky A., Ladner M. B., Stanley E. R. Apparent role of the macrophage growth factor, CSF-1, in placental development. Nature. 1987 Dec 3;330(6147):484–486. doi: 10.1038/330484a0. [DOI] [PubMed] [Google Scholar]
  37. Pontzer C. H., Torres B. A., Vallet J. L., Bazer F. W., Johnson H. M. Antiviral activity of the pregnancy recognition hormone ovine trophoblast protein-1. Biochem Biophys Res Commun. 1988 Apr 29;152(2):801–807. doi: 10.1016/s0006-291x(88)80109-8. [DOI] [PubMed] [Google Scholar]
  38. Raj N. B., Engelhardt J., Au W. C., Levy D. E., Pitha P. M. Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation. J Biol Chem. 1989 Oct 5;264(28):16658–16666. [PubMed] [Google Scholar]
  39. Raj N. B., Israeli R., Kellum M., Pitha P. M. Upstream regulatory elements of murine alpha 4-interferon gene confer inducibility and cell type-restricted expression. J Biol Chem. 1989 Jul 5;264(19):11149–11157. [PubMed] [Google Scholar]
  40. Rappolee D. A., Mark D., Banda M. J., Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988 Aug 5;241(4866):708–712. doi: 10.1126/science.3041594. [DOI] [PubMed] [Google Scholar]
  41. Roberts R. M., Imakawa K., Niwano Y., Kazemi M., Malathy P. V., Hansen T. R., Glass A. A., Kronenberg L. H. Interferon production by the preimplantation sheep embryo. J Interferon Res. 1989 Apr;9(2):175–187. doi: 10.1089/jir.1989.9.175. [DOI] [PubMed] [Google Scholar]
  42. Shirono H., Kono K., Koga J., Hayashi S., Matsuo A., Hiratani H. Existence and unique N-terminal sequence of alpha II (omega) interferon in natural leukocyte interferon preparation. Biochem Biophys Res Commun. 1990 Apr 16;168(1):16–21. doi: 10.1016/0006-291x(90)91668-i. [DOI] [PubMed] [Google Scholar]
  43. Stewart H. J., McCann S. H., Flint A. P. Structure of an interferon-alpha 2 gene expressed in the bovine conceptus early in gestation. J Mol Endocrinol. 1990 Jun;4(3):275–282. doi: 10.1677/jme.0.0040275. [DOI] [PubMed] [Google Scholar]
  44. Tovey M. G., Streuli M., Gresser I., Gugenheim J., Blanchard B., Guymarho J., Vignaux F., Gigou M. Interferon messenger RNA is produced constitutively in the organs of normal individuals. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5038–5042. doi: 10.1073/pnas.84.14.5038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Weidle U., Weissmann C. The 5'-flanking region of a human IFN-alpha gene mediates viral induction of transcription. Nature. 1983 Jun 2;303(5916):442–446. doi: 10.1038/303442a0. [DOI] [PubMed] [Google Scholar]
  46. Xanthoudakis S., Cohen L., Hiscott J. Multiple protein-DNA interactions within the human interferon-beta regulatory element. J Biol Chem. 1989 Jan 15;264(2):1139–1145. [PubMed] [Google Scholar]

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