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Isolation and characterization of a novel mutant mouse cell line resistant to Newcastle disease virus: constitutive interferon production and enhanced interferon sensitivity

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Summary

In our attempt to isolate mutant cell lines resistant to Newcastle disease virus (NDV) we developed an improved procedure for enrichment of NDV-resistant cells from mouse FM3A cells and isolated a novel NDV-resistant mutant cell line, Had-2, with characteristics different from Had-1, a previously reported NDV-receptor-deficient mutant strain. Had-2 cells adsorbed NDV normally but the accumulation of viral mRNAs and proteins was inhibited. Had-2 cells had to be grown at higher cell densities in order to be NDV-resistant, and it was revealed that they did not exhibit NDV-resistance when grown at lower cell densities. A conditioned medium prepared from a culture of Had-2 cells grown at high cell density was able to make a low-density culture NDV-resistant. The activity of the conditioned medium to induce NDV-resistance was completely neutralized by addition of both anti interferon (IFN)-α and anti IFN-β antibodies, indicating that Had-2 cells were constitutively releasing IFNs, though their levels were rather low. Had-2 cells were also characterized by an increased sensitivity to IFNs as compared with the parental FM3A cells, since the conditioned medium containing IFNs did not render FM3A cells resistant to NDV.

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References

  1. Banfield BW, Tufaro F (1990) Herpes simplex virus particles are unable to traverse the secretory pathway in the mouse L-cell mutant gro29. J Virol 64: 5716–5729

    Google Scholar 

  2. Darnell JE Jr, Sawyer TK (1960) The basis for variation in susceptibility to poliovirus in HeLa cells. Virology 11: 665–675.

    Google Scholar 

  3. Fujita T, Kimura Y, Miyamoto M, Barsoumian EL, Taniguchi T (1989) Induction of endogenous IFN-α and IFN-β genes by a regulatory transcription factor, IRF-1. Nature 337: 270–272

    Google Scholar 

  4. Hara T, Hattori S, Kawakita M (1989) Isolation and characterization of mouse FM3A cell mutants which are devoid of Newcastle disease virus receptors. J Virol 63: 182–188

    Google Scholar 

  5. Hara T, Endo T, Furukawa K, Kawakita M, Kobata A (1989) Elucidation of the phenotypic change on the surface of Had-1 cell, a mutant cell line of mouse FM3A carcinoma cells selected by resistance to Newcastle disease virus infection. J Biochem 106: 236–247

    Google Scholar 

  6. Hara T, Yamauchi M, Takahashi E, Hoshino M, Aoki K, Ayusawa D, Kawakita M (1993) The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus. Somat Cell Genet 19: 571–575

    Google Scholar 

  7. Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, Taniguchi T (1990) Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell 63: 303–312

    Google Scholar 

  8. Hoshino M, Taira H, Hattori S, Kawakita M (1987) The target reaction in the antiviral action of mouse interferon against vesicular stomatitis virus multiplication. J Biochem 101: 685–694

    Google Scholar 

  9. Inocencio NM, Moehring JM, Moehring TJ (1993) A mutant CHO-K1 strain with resistance toPseudomonas exotoxin A is unable to process the precursor fusion glycoprotein of Newcastle disease virus. J Virol 67: 593–595

    Google Scholar 

  10. Ishida N, Taira H, Omata T, Mizumoto K, Hattori S, Iwasaki K, Kawakita M (1986) Sequence of 2, 617 nucleotides from the 3′ end of Newcastle disease virus genome RNA and the predicted amino acid sequence of viral NP protein. Nucleic Acids Res 14: 6551–6564

    Google Scholar 

  11. Jarvis AP, Colby C (1978) Murine interferon system regulation: isolation and characterization of a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon. Cell 14: 355–363

    Google Scholar 

  12. Jarvis AP, White C, Ball A, Gupta SL, Ratner L, Sen GC, Colby C (1978) Interferon-associated, dsRNA-dependent enzyme activities in a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon. Cell 14: 879–887

    Google Scholar 

  13. John J, McKendry R, Pellegrini S, Flavell D, Kerr IM, Stark GR (1991) Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons. Mol Cell Biol 11: 4189–4195

    Google Scholar 

  14. Kaplan G, Levy A, Racaniello VR (1989) Isolation and characterization of HeLa cell lines blocked at different steps in the poliovirus life cycle. J Virol 63: 43–51

    Google Scholar 

  15. Kimura Y, Yokochi T, Miyadai T, Yoshida K, Yokoo J, Matsumoto K (1985) Characterization of a porcine kidney cell line resistant to influenza virus infection. J Virol 53: 980–983

    Google Scholar 

  16. Koyama H, Ayusawa D, Okawa M, Takatsuki A, Tamura G (1982) Tunicamycin-resistant mutations in mouse FM3A cells. Mutat Res 96: 243–258

    Google Scholar 

  17. Koyama H, Kodama H (1982) Adenine phosphoribosyltransferase deficiency in cultured mouse mammary tumor FM3A cells resistant to 4-carbamoylimidazolium 5-olate. Cancer Res 42: 4210–4214

    Google Scholar 

  18. Kuge O, Akamatsu Y, Nishijima M (1989) Abortive infection with sindbis virus of a chinese hamster ovary cell mutant defective in phosphatidylserine and phosphatidy-lethanolamine biosynthesis. Biochim Biophys Acta 986: 61–69

    Google Scholar 

  19. McKendry R, John J, Flavell D, Müller M, Kerr IM, Stark GR (1991) High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both α and γ interferons. Proc Natl Acad Sci USA 88: 11455–11459

    Google Scholar 

  20. McKendry R, Pellegrini S, Kerr IM, Stark GR (1994) Constitutive production of alpha and beta interferons in mutant human cell lines. J Virol 68: 4057–4062

    Google Scholar 

  21. Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (1988) Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements. Cell 54: 903–913

    Google Scholar 

  22. Moehring JM, Moehring TJ (1983) Strains of CHO-K1 cells resistant toPseudomonas exotoxin A and cross-resistant to diphtheria toxin and viruses. Infect Immun 41: 998–1009

    Google Scholar 

  23. Moehring TJ, Moehring JM (1976) Interaction of diphtheria toxin and its active subunit, fragment A, with toxin-sensitive and toxin-resistant cells. Infect Immun 13: 1426–1432

    Google Scholar 

  24. Morgan MJ, Colby C, Hulse JLN (1973) Isolation and characterization of virus-resistant mouse embryo fibroblasts. J Gen Virol 20: 377–385

    Google Scholar 

  25. Müller M, Briscoe J, Laxton C, guschin D, Ziemiecki A, Silvennoinen O, Harpur AG, Barbieri G, Witthuhn BA, Schindler C, Pellegrini S, Wilks AF, Ihle JN, Stark GR, Kerr IM (1993) The protein tyrosine kinase JAK1 complements defects in interferon-α/β and-γ signal transduction. Nature 366: 129–135

    Google Scholar 

  26. Müller M, Laxton C, Briscoe J, Schindler C, Improta T, Darnell JE Jr, Stark GR, Kerr IM (1993) Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-α and-γ signal transduction pathways. EMBO J 12: 4221–4228

    Google Scholar 

  27. Ono M, Mifune K, Yoshimura A, Ohnishi S, Kuwano M (1985) Monensin-resistant mouse Balb/3T3 cell mutant with aberrant penetration of vesicular stomatitis virus. J Cell Biol 101: 60–65

    Google Scholar 

  28. Pellegrini S, John J, Shearer M, Kerr IM, Stark GR (1989) Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway. Mol Cell Biol 9: 4605–4612

    Google Scholar 

  29. Reis LFL, Harada H, Wolchok JD, Taniguchi T, Vilček J (1992) Critical role of a common transcription factor, IRF-1, in the regulation of IFN-β and IFN-inducible genes. EMBO J 11: 185–193

    Google Scholar 

  30. Robbins AR, Peng SS, Marshall JL (1983) Mutant chinese hamster ovary cells pleiotropically defective in receptor-mediated endocytosis. J Cell Biol 96: 1064–1071

    Google Scholar 

  31. Robbins AR, Oliver C, Bateman JL, Krag SS, Galloway CJ, Mellman I (1984) A single mutation in chinese hamster ovary cells impairs both Golgi and endosomal functions. J Cell Biol 99: 1296–1308

    Google Scholar 

  32. Shieh M-T, WuDunn D, Montgomery RI, Esko JD, Spear PG (1992) Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol 116: 1273–1281

    Google Scholar 

  33. Tufaro F, Snider MD, McKnight SL (1987) Identification and characterization of a mouse cell mutant defective in the intracellular transport of glycoproteins. J Cell Biol 105: 647–657

    Google Scholar 

  34. Velazquez L, Fellous M, Stark GR, Pellegrini S (1992) A protein tyrosine kinase in the interferon α/β signaling pathway. Cell 70: 313–322

    Google Scholar 

  35. Wang R-H, Colbaugh PA, Kao C-Y, Rutledge EA, Draper RK (1990) Impaired secretion and fluid-phase endocytosis in the End4 mutant of chinese hamster ovary cells. J Biol Chem 265: 20179–20187

    Google Scholar 

  36. Watson DG, Moehring JM, Moehring TJ (1991) A mutant CHO-K1 strain with resistance toPseudomonas exotoxin A and alphaviruses fails to cleave sindbis virus glycoprotein PE2. J Virol 65: 2332–2339

    Google Scholar 

  37. Whealy ME, Robbins AK, Tufaro F, Enquist LW (1992) A cellular function is required for pseudorabies virus envelope glycoprotein processing and virus egress. J Virol 66: 3803–3810

    Google Scholar 

  38. Wilson JH, DePamphilis M, Berg P (1976) Simian virus 40-permissive cell interactions: selection and characterization of spontaneously arising monkey cells that are resistant to simian virus 40 infection. J Virol 20: 391–399

    Google Scholar 

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Aoki, K., Oh-hira, M., Hoshino, M. et al. Isolation and characterization of a novel mutant mouse cell line resistant to Newcastle disease virus: constitutive interferon production and enhanced interferon sensitivity. Archives of Virology 139, 337–350 (1994). https://doi.org/10.1007/BF01310796

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  • DOI: https://doi.org/10.1007/BF01310796

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