Abstract
Vesicular stomatitis virus (VSV) has a broad host range. It replicates in the cytoplasm and causes rapid cytopathic effects. We show that following VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many cell types. This factor, tentatively called VSV-induced binding protein (VIBP), was estimated to have an approximate molecular mass of 50 kDa and was distinct from known members of the interferon regulatory factor family, that are known to bind to the ISRE. Induction of VIBP required tyrosine kinase activity but did not require cellular transcription. Treatment of cells with cycloheximide, which inhibits translation, only partially inhibited induction of VIBP. However, type I interferons and staurosporine, both of which inhibit VSV transcription, inhibited VIBP induction. Moreover, a double-stranded RNA analog, poly(I)-poly(C) also induced a DNA-binding activity very similar to that of VIBP. These results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral transcripts. The functional activity of VIBP was analyzed in cells stably transfected with a herpesvirus thymidine kinase-luciferase reporter gene that is under control of the ISRE. While activity of the control promoter without ISRE was strongly inhibited following VSV infection (as a result of virus-mediated transcriptional shutdown of the host cell), the inhibition was reversed by the ISRE-containing promoter, albeit partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other cells tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility.
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- Banerjee A. K. Transcription and replication of rhabdoviruses. Microbiol Rev. 1987 Mar;51(1):66–87. doi: 10.1128/mr.51.1.66-87.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belkowski L. S., Sen G. C. Inhibition of vesicular stomatitis viral mRNA synthesis by interferons. J Virol. 1987 Mar;61(3):653–660. doi: 10.1128/jvi.61.3.653-660.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Black B. L., Lyles D. S. Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo. J Virol. 1992 Jul;66(7):4058–4064. doi: 10.1128/jvi.66.7.4058-4064.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blondel D., Harmison G. G., Schubert M. Role of matrix protein in cytopathogenesis of vesicular stomatitis virus. J Virol. 1990 Apr;64(4):1716–1725. doi: 10.1128/jvi.64.4.1716-1725.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bovolenta C., Driggers P. H., Marks M. S., Medin J. A., Politis A. D., Vogel S. N., Levy D. E., Sakaguchi K., Appella E., Coligan J. E. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046–5050. doi: 10.1073/pnas.91.11.5046. [DOI] [PMC free article] [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]
- Cohen P., Klumpp S., Schelling D. L. An improved procedure for identifying and quantitating protein phosphatases in mammalian tissues. FEBS Lett. 1989 Jul 3;250(2):596–600. doi: 10.1016/0014-5793(89)80803-8. [DOI] [PubMed] [Google Scholar]
- Daly C., Reich N. C. Double-stranded RNA activates novel factors that bind to the interferon-stimulated response element. Mol Cell Biol. 1993 Jun;13(6):3756–3764. doi: 10.1128/mcb.13.6.3756. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
- Driggers P. H., Ennist D. L., Gleason S. L., Mak W. H., Marks M. S., Levi B. Z., Flanagan J. R., Appella E., Ozato K. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1990 May;87(10):3743–3747. doi: 10.1073/pnas.87.10.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunigan D. D., Baird S., Lucas-Lenard J. Lack of correlation between the accumulation of plus-strand leader RNA and the inhibition of protein and RNA synthesis in vesicular stomatitis virus infected mouse L cells. Virology. 1986 Apr 15;150(1):231–246. doi: 10.1016/0042-6822(86)90282-5. [DOI] [PubMed] [Google Scholar]
- Edery I., Petryshyn R., Sonenberg N. Activation of double-stranded RNA-dependent kinase (dsl) by the TAR region of HIV-1 mRNA: a novel translational control mechanism. Cell. 1989 Jan 27;56(2):303–312. doi: 10.1016/0092-8674(89)90904-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Gaccione C., Marcus P. I. Interferon induction by viruses. XVIII. Vesicular stomatitis virus-New Jersey: a single infectious particle can both induce and suppress interferon production. J Interferon Res. 1989 Oct;9(5):603–614. doi: 10.1089/jir.1989.9.603. [DOI] [PubMed] [Google Scholar]
- Grinnell B. W., Wagner R. R. Nucleotide sequence and secondary structure of VSV leader RNA and homologous DNA involved in inhibition of DNA-dependent transcription. Cell. 1984 Feb;36(2):533–543. doi: 10.1016/0092-8674(84)90246-0. [DOI] [PubMed] [Google Scholar]
- Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
- Harada H., Willison K., Sakakibara J., Miyamoto M., Fujita T., Taniguchi T. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell. 1990 Oct 19;63(2):303–312. doi: 10.1016/0092-8674(90)90163-9. [DOI] [PubMed] [Google Scholar]
- Hug H., Costas M., Staeheli P., Aebi M., Weissmann C. Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter. Mol Cell Biol. 1988 Aug;8(8):3065–3079. doi: 10.1128/mcb.8.8.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalvakolanu D. V., Sen G. C. Differentiation-dependent activation of interferon-stimulated gene factors and transcription factor NF-kappa B in mouse embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3167–3171. doi: 10.1073/pnas.90.8.3167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kang C. Y., Prevec L. Proteins of vesicular stomatitis virus. 3. Intracellular synthesis and extracellular appearance of virus-specific proteins. Virology. 1971 Dec;46(3):678–690. doi: 10.1016/0042-6822(71)90070-5. [DOI] [PubMed] [Google Scholar]
- Kanno Y., Kozak C. A., Schindler C., Driggers P. H., Ennist D. L., Gleason S. L., Darnell J. E., Jr, Ozato K. The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Mol Cell Biol. 1993 Jul;13(7):3951–3963. doi: 10.1128/mcb.13.7.3951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessler D. S., Levy D. E. Protein kinase activity required for an early step in interferon-alpha signaling. J Biol Chem. 1991 Dec 5;266(34):23471–23476. [PubMed] [Google Scholar]
- Kumar A., Haque J., Lacoste J., Hiscott J., Williams B. R. Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6288–6292. doi: 10.1073/pnas.91.14.6288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurilla M. G., Piwnica-Worms H., Keene J. D. Rapid and transient localization of the leader RNA of vesicular stomatitis virus in the nuclei of infected cells. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5240–5244. doi: 10.1073/pnas.79.17.5240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levy D. E., Kessler D. S., Pine R., Reich N., Darnell J. E., Jr Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988 Apr;2(4):383–393. doi: 10.1101/gad.2.4.383. [DOI] [PubMed] [Google Scholar]
- Lew D. J., Decker T., Strehlow I., Darnell J. E. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. Mol Cell Biol. 1991 Jan;11(1):182–191. doi: 10.1128/mcb.11.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lyles D. S., Puddington L., McCreedy B. J., Jr Vesicular stomatitis virus M protein in the nuclei of infected cells. J Virol. 1988 Nov;62(11):4387–4392. doi: 10.1128/jvi.62.11.4387-4392.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Marcus P. I., Engelhardt D. L., Hunt J. M., Sekellick M. J. Interferon action: inhibition of vesicular stomatitis virus RNA synthesis induced by virion-bound polymerase. Science. 1971 Nov 5;174(4009):593–598. doi: 10.1126/science.174.4009.593. [DOI] [PubMed] [Google Scholar]
- Marcus P. I., Sekellick M. J. Interferon action III. The rate of primary transcription of vesicular stomatitis virus is inhibited by interferon action. J Gen Virol. 1978 Mar;38(3):391–408. doi: 10.1099/0022-1317-38-3-391. [DOI] [PubMed] [Google Scholar]
- Marcus P. I., Sekellick M. J., Nichol S. T. Interferon induction by viruses. XXI. Vesicular stomatitis virus: interferon inducibility as a phylogenetic marker. J Interferon Res. 1992 Aug;12(4):297–305. doi: 10.1089/jir.1992.12.297. [DOI] [PubMed] [Google Scholar]
- Marvaldi J. L., Lucas-Lenard J., Sekellick M. J., Marcus P. I. Cell killing by viruses. IV. Cell killing and protein synthesis inhibition by vesicular stomatitis virus require the same gene functions. Virology. 1977 Jun 15;79(2):267–280. doi: 10.1016/0042-6822(77)90354-3. [DOI] [PubMed] [Google Scholar]
- Masters P. S., Samuel C. E. Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human leukocyte interferon. II. Effect on viral macromolecular synthesis. J Biol Chem. 1983 Oct 10;258(19):12026–12033. [PubMed] [Google Scholar]
- Matsuyama T., Kimura T., Kitagawa M., Pfeffer K., Kawakami T., Watanabe N., Kündig T. M., Amakawa R., Kishihara K., Wakeham A. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell. 1993 Oct 8;75(1):83–97. [PubMed] [Google Scholar]
- McGowan J. J., Emerson S. U., Wagner R. R. The plus-strand leader RNA of VSV inhibits DNA-dependent transcription of adenovirus and SV40 genes in a soluble whole-cell extract. Cell. 1982 Feb;28(2):325–333. doi: 10.1016/0092-8674(82)90350-6. [DOI] [PubMed] [Google Scholar]
- Meurs E., Chong K., Galabru J., Thomas N. S., Kerr I. M., Williams B. R., Hovanessian A. G. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990 Jul 27;62(2):379–390. doi: 10.1016/0092-8674(90)90374-n. [DOI] [PubMed] [Google Scholar]
- Minucci S., Zand D. J., Dey A., Marks M. S., Nagata T., Grippo J. F., Ozato K. Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells. Mol Cell Biol. 1994 Jan;14(1):360–372. doi: 10.1128/mcb.14.1.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molitor J. A., Walker W. H., Doerre S., Ballard D. W., Greene W. C. NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10028–10032. doi: 10.1073/pnas.87.24.10028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller M., Briscoe J., Laxton C., Guschin D., Ziemiecki A., Silvennoinen O., Harpur A. G., Barbieri G., Witthuhn B. A., Schindler C. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993 Nov 11;366(6451):129–135. doi: 10.1038/366129a0. [DOI] [PubMed] [Google Scholar]
- Nelson N., Marks M. S., Driggers P. H., Ozato K. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol Cell Biol. 1993 Jan;13(1):588–599. doi: 10.1128/mcb.13.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paik S. Y., Banerjea A. C., Harmison G. G., Chen C. J., Schubert M. Inducible and conditional inhibition of human immunodeficiency virus proviral expression by vesicular stomatitis virus matrix protein. J Virol. 1995 Jun;69(6):3529–3537. doi: 10.1128/jvi.69.6.3529-3537.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parrington J., Rogers N. C., Gewert D. R., Pine R., Veals S. A., Levy D. E., Stark G. R., Kerr I. M. The interferon-stimulable response elements of two human genes detect overlapping sets of transcription factors. Eur J Biochem. 1993 Jun 15;214(3):617–626. doi: 10.1111/j.1432-1033.1993.tb17961.x. [DOI] [PubMed] [Google Scholar]
- Reich N., Pine R., Levy D., Darnell J. E., Jr Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products. J Virol. 1988 Jan;62(1):114–119. doi: 10.1128/jvi.62.1.114-119.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reis L. F., Ruffner H., Stark G., Aguet M., Weissmann C. Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes. EMBO J. 1994 Oct 17;13(20):4798–4806. doi: 10.1002/j.1460-2075.1994.tb06805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigaut K. D., Gao Y., Lenard J. Effects of staurosporine on transcription by vesicular stomatitis virus. Virology. 1993 Jun;194(2):433–440. doi: 10.1006/viro.1993.1282. [DOI] [PubMed] [Google Scholar]
- Schindler C., Fu X. Y., Improta T., Aebersold R., Darnell J. E., Jr Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836–7839. doi: 10.1073/pnas.89.16.7836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sen G. C., Herz R. E. Differential antiviral effects of interferon in three murine cell lines. J Virol. 1983 Mar;45(3):1017–1027. doi: 10.1128/jvi.45.3.1017-1027.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sen G. C., Lengyel P. The interferon system. A bird's eye view of its biochemistry. J Biol Chem. 1992 Mar 15;267(8):5017–5020. [PubMed] [Google Scholar]
- SenGupta D. N., Silverman R. H. Activation of interferon-regulated, dsRNA-dependent enzymes by human immunodeficiency virus-1 leader RNA. Nucleic Acids Res. 1989 Feb 11;17(3):969–978. doi: 10.1093/nar/17.3.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staeheli P., Pavlovic J. Inhibition of vesicular stomatitis virus mRNA synthesis by human MxA protein. J Virol. 1991 Aug;65(8):4498–4501. doi: 10.1128/jvi.65.8.4498-4501.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thacore H. R. Effect of interferon on transcription and translation of vesicular stomatitis virus in human and simian cell cultures. J Gen Virol. 1978 Nov;41(2):421–426. doi: 10.1099/0022-1317-41-2-421. [DOI] [PubMed] [Google Scholar]
- Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]
- Tiwari R. K., Kusari J., Kumar R., Sen G. C. Gene induction by interferons and double-stranded RNA: selective inhibition by 2-aminopurine. Mol Cell Biol. 1988 Oct;8(10):4289–4294. doi: 10.1128/mcb.8.10.4289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veals S. A., Schindler C., Leonard D., Fu X. Y., Aebersold R., Darnell J. E., Jr, Levy D. E. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992 Aug;12(8):3315–3324. doi: 10.1128/mcb.12.8.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weck P. K., Wagner R. R. Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus. J Virol. 1978 Mar;25(3):770–780. doi: 10.1128/jvi.25.3.770-780.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weisz A., Marx P., Sharf R., Appella E., Driggers P. H., Ozato K., Levi B. Z. Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. J Biol Chem. 1992 Dec 15;267(35):25589–25596. [PubMed] [Google Scholar]
- Wertz G. W., Levine M. RNA synthesis by vesicular stomatitis virus and a small plaque mutant: effects of cycloheximide. J Virol. 1973 Aug;12(2):253–264. doi: 10.1128/jvi.12.2.253-264.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wertz G. W., Youngner J. S. Inhibition of protein synthesis in L cells infected with vesicular stomatitis virus. J Virol. 1972 Jan;9(1):85–89. doi: 10.1128/jvi.9.1.85-89.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitaker-Dowling P., Youngner J. S. Alteration of vesicular stomatitis virus L and NS proteins by uv irradiation: implications for the mechanism of host cell shut-off. Virology. 1988 May;164(1):171–175. doi: 10.1016/0042-6822(88)90633-2. [DOI] [PubMed] [Google Scholar]
- Wu F. S., Lucas-Lenard J. M. Inhibition of ribonucleic acid accumulation in mouse L cells infected with vesicular stomatitis virus requires viral ribonucleic acid transcription. Biochemistry. 1980 Feb 19;19(4):804–810. doi: 10.1021/bi00545a029. [DOI] [PubMed] [Google Scholar]
- Yamaki H., Iguchi-Ariga S. M., Ariga H. Inhibition of c-myc gene expression in murine lymphoblastoma cells by geldanamycin and herbimycin, antibiotics of benzoquinoid ansamycin group. J Antibiot (Tokyo) 1989 Apr;42(4):604–610. doi: 10.7164/antibiotics.42.604. [DOI] [PubMed] [Google Scholar]
- Zhou A., Hassel B. A., Silverman R. H. Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action. Cell. 1993 Mar 12;72(5):753–765. doi: 10.1016/0092-8674(93)90403-d. [DOI] [PubMed] [Google Scholar]