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.
Similar content being viewed by others
References
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
Darnell JE Jr, Sawyer TK (1960) The basis for variation in susceptibility to poliovirus in HeLa cells. Virology 11: 665–675.
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
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
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
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
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
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
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
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
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
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
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
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
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
Koyama H, Ayusawa D, Okawa M, Takatsuki A, Tamura G (1982) Tunicamycin-resistant mutations in mouse FM3A cells. Mutat Res 96: 243–258
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
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
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
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
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
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
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
Morgan MJ, Colby C, Hulse JLN (1973) Isolation and characterization of virus-resistant mouse embryo fibroblasts. J Gen Virol 20: 377–385
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
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
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
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
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
Robbins AR, Peng SS, Marshall JL (1983) Mutant chinese hamster ovary cells pleiotropically defective in receptor-mediated endocytosis. J Cell Biol 96: 1064–1071
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
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
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
Velazquez L, Fellous M, Stark GR, Pellegrini S (1992) A protein tyrosine kinase in the interferon α/β signaling pathway. Cell 70: 313–322
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
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
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
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01310796