Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Aug;70(8):4904–4913. doi: 10.1128/jvi.70.8.4904-4913.1996

The adenovirus E3-14.7K protein and the E3-10.4K/14.5K complex of proteins, which independently inhibit tumor necrosis factor (TNF)-induced apoptosis, also independently inhibit TNF-induced release of arachidonic acid.

P Krajcsi 1, T Dimitrov 1, T W Hermiston 1, A E Tollefson 1, T S Ranheim 1, S B Vande Pol 1, A H Stephenson 1, W S Wold 1
PMCID: PMC190440  PMID: 8763993

Abstract

Tumor necrosis factor (TNF) is an inflammatory cytokine that inhibits the replication of many viruses in cultured cells. We have reported that adenovirus (Ad) infection of TNF-resistant mouse cells renders them susceptible to lysis by TNF and that two sets of proteins encoded by the E3 transcription unit block TNF cytolysis. The E3 protein sets are named E3-14.7K (14,700 kDa) and E3-10.4K/14.5K (a complex of two proteins of 10,400 and 14,500 kDa). TNF activation of the 85-kDa cytosolic phospholipase A2 (cPLA2) is thought to be essential for TNF cytolysis (i.e.,TNF-induced apoptosis). Here we provide evidence that cPLA2 is important in the response of Ad-infected cells to TNF and that the mechanism by which E3-14.7K and E3-10.4K/14.5K inhibit TNF cytolysis is by inhibiting TNF activation of cPLA2. cPLA2 cleaves arachidonic acid (AA) specifically from membrane phospholipids; therefore, cPLA2 activity was measured by the release of 3H-AA from cells prelabeled with 3H-AA. Uninfected cells or cells infected with wild-type Ad were not lysed and did not release 3H-AA in response to TNF. In contrast, TNF treatment induced cytolysis and 3H-AA release in uninfected cells sensitized to TNF by treatment with cycloheximide and also in infected cells sensitized to TNF by expression of E1A. In C127 cells, in which either E3-14.7K or E3-10.4K/14.5K inhibits TNF cytolysis, either set of proteins inhibited TNF-induced release of 3H-AA. In C3HA cells, in which E3-14.7K but not E3-10.4K/14.5K prevents TNF cytolysis, E3-14.7K but not E3-10.4K/14.5K prevented TNF-induced release of 3H-AA. When five virus mutants with lesions in E3-14.7K were examined, there was a perfect correlation between a mutant's ability to inhibit both TNF-induced cytolysis and release of 3H-AA. E3-14.7K expressed in two stably transfected C127 cell lines prevented both TNF-cycloheximide-induced cytolysis and release of 3H-AA. The E3 proteins also prevented TNF-induced cytolysis and release of 3H-AA in mouse L929 cells, which are spontaneously sensitive to TNF. TNF cytolysis was blocked by dexamethasone, an inhibitor of PLA2 activity, and by nordihydroquaiaretic acid, which inhibits the metabolism of AA to the leukotrienes. Indomethacin, which blocks the formation of prostaglandins from AA, did not inhibit TNF cytolysis. The leukotrienes and prostaglandins are amplifiers of the inflammatory response. We propose that E3-14.7K and E3-10.4K/14.5K function independently in Ad infection to inhibit both cytolysis and inflammation induced by TNF.

Full Text

The Full Text of this article is available as a PDF (291.3 KB).

Selected References

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

  1. Ames R. S., Holskin B., Mitcho M., Shalloway D., Chen M. J. Induction of sensitivity to the cytotoxic action of tumor necrosis factor alpha by adenovirus E1A is independent of transformation and transcriptional activation. J Virol. 1990 Sep;64(9):4115–4122. doi: 10.1128/jvi.64.9.4115-4122.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baumann H., Gauldie J. The acute phase response. Immunol Today. 1994 Feb;15(2):74–80. doi: 10.1016/0167-5699(94)90137-6. [DOI] [PubMed] [Google Scholar]
  3. Beetens J. R., Loots W., Somers Y., Coene M. C., De Clerck F. Ketoconazole inhibits the biosynthesis of leukotrienes in vitro and in vivo. Biochem Pharmacol. 1986 Mar 15;35(6):883–891. doi: 10.1016/0006-2952(86)90072-9. [DOI] [PubMed] [Google Scholar]
  4. Billah M. M., Bryant R. W., Siegel M. I. Lipoxygenase products of arachidonic acid modulate biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by human neutrophils via phospholipase A2. J Biol Chem. 1985 Jun 10;260(11):6899–6906. [PubMed] [Google Scholar]
  5. Brady H. A., Scaria A., Wold W. S. Map of cis-acting sequences that determine alternative pre-mRNA processing in the E3 complex transcription unit of adenovirus. J Virol. 1992 Oct;66(10):5914–5923. doi: 10.1128/jvi.66.10.5914-5923.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brady H. A., Wold W. S. Identification of a novel sequence that governs both polyadenylation and alternative splicing in region E3 of adenovirus. Nucleic Acids Res. 1987 Nov 25;15(22):9397–9416. doi: 10.1093/nar/15.22.9397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen M. J., Holskin B., Strickler J., Gorniak J., Clark M. A., Johnson P. J., Mitcho M., Shalloway D. Induction by E1A oncogene expression of cellular susceptibility to lysis by TNF. Nature. 1987 Dec 10;330(6148):581–583. doi: 10.1038/330581a0. [DOI] [PubMed] [Google Scholar]
  8. Chiou S. K., Tseng C. C., Rao L., White E. Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells. J Virol. 1994 Oct;68(10):6553–6566. doi: 10.1128/jvi.68.10.6553-6566.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark J. D., Lin L. L., Kriz R. W., Ramesha C. S., Sultzman L. A., Lin A. Y., Milona N., Knopf J. L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043–1051. doi: 10.1016/0092-8674(91)90556-e. [DOI] [PubMed] [Google Scholar]
  10. Decker T., Lohmann-Matthes M. L. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988 Nov 25;115(1):61–69. doi: 10.1016/0022-1759(88)90310-9. [DOI] [PubMed] [Google Scholar]
  11. Dennis E. A. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem. 1994 May 6;269(18):13057–13060. [PubMed] [Google Scholar]
  12. Duerksen-Hughes P. J., Hermiston T. W., Wold W. S., Gooding L. R. The amino-terminal portion of CD1 of the adenovirus E1A proteins is required to induce susceptibility to tumor necrosis factor cytolysis in adenovirus-infected mouse cells. J Virol. 1991 Mar;65(3):1236–1244. doi: 10.1128/jvi.65.3.1236-1244.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Duerksen-Hughes P., Wold W. S., Gooding L. R. Adenovirus E1A renders infected cells sensitive to cytolysis by tumor necrosis factor. J Immunol. 1989 Dec 15;143(12):4193–4200. [PubMed] [Google Scholar]
  14. Durstin M., Durstin S., Molski T. F., Becker E. L., Sha'afi R. I. Cytoplasmic phospholipase A2 translocates to membrane fraction in human neutrophils activated by stimuli that phosphorylate mitogen-activated protein kinase. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3142–3146. doi: 10.1073/pnas.91.8.3142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ginsberg H. S., Lundholm-Beauchamp U., Horswood R. L., Pernis B., Wold W. S., Chanock R. M., Prince G. A. Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proc Natl Acad Sci U S A. 1989 May;86(10):3823–3827. doi: 10.1073/pnas.86.10.3823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ginsberg H. S., Moldawer L. L., Sehgal P. B., Redington M., Kilian P. L., Chanock R. M., Prince G. A. A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1651–1655. doi: 10.1073/pnas.88.5.1651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gooding L. R., Aquino L., Duerksen-Hughes P. J., Day D., Horton T. M., Yei S. P., Wold W. S. The E1B 19,000-molecular-weight protein of group C adenoviruses prevents tumor necrosis factor cytolysis of human cells but not of mouse cells. J Virol. 1991 Jun;65(6):3083–3094. doi: 10.1128/jvi.65.6.3083-3094.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gooding L. R., Elmore L. W., Tollefson A. E., Brady H. A., Wold W. S. A 14,700 MW protein from the E3 region of adenovirus inhibits cytolysis by tumor necrosis factor. Cell. 1988 May 6;53(3):341–346. doi: 10.1016/0092-8674(88)90154-7. [DOI] [PubMed] [Google Scholar]
  19. Gooding L. R., Ranheim T. S., Tollefson A. E., Aquino L., Duerksen-Hughes P., Horton T. M., Wold W. S. The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus function together to protect many but not all mouse cell lines against lysis by tumor necrosis factor. J Virol. 1991 Aug;65(8):4114–4123. doi: 10.1128/jvi.65.8.4114-4123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gooding L. R. Regulation of TNF-mediated cell death and inflammation by human adenoviruses. Infect Agents Dis. 1994 Apr-Jun;3(2-3):106–115. [PubMed] [Google Scholar]
  21. Gooding L. R., Sofola I. O., Tollefson A. E., Duerksen-Hughes P., Wold W. S. The adenovirus E3-14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. J Immunol. 1990 Nov 1;145(9):3080–3086. [PubMed] [Google Scholar]
  22. Gooding L. R., Wold W. S. Molecular mechanisms by which adenoviruses counteract antiviral immune defenses. Crit Rev Immunol. 1990;10(1):53–71. [PubMed] [Google Scholar]
  23. Green M., Wold W. S. Human adenoviruses: growth, purification, and transfection assay. Methods Enzymol. 1979;58:425–435. doi: 10.1016/s0076-6879(79)58157-9. [DOI] [PubMed] [Google Scholar]
  24. Haliday E. M., Ramesha C. S., Ringold G. TNF induces c-fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite. EMBO J. 1991 Jan;10(1):109–115. doi: 10.1002/j.1460-2075.1991.tb07926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hannun Y. A. The sphingomyelin cycle and the second messenger function of ceramide. J Biol Chem. 1994 Feb 4;269(5):3125–3128. [PubMed] [Google Scholar]
  26. Hansen M. B., Nielsen S. E., Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989 May 12;119(2):203–210. doi: 10.1016/0022-1759(89)90397-9. [DOI] [PubMed] [Google Scholar]
  27. Hayakawa M., Ishida N., Takeuchi K., Shibamoto S., Hori T., Oku N., Ito F., Tsujimoto M. Arachidonic acid-selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor. J Biol Chem. 1993 May 25;268(15):11290–11295. [PubMed] [Google Scholar]
  28. Heller R. A., Krönke M. Tumor necrosis factor receptor-mediated signaling pathways. J Cell Biol. 1994 Jul;126(1):5–9. doi: 10.1083/jcb.126.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hoeck W. G., Ramesha C. S., Chang D. J., Fan N., Heller R. A. Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4475–4479. doi: 10.1073/pnas.90.10.4475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hoffman P., Yaffe M. B., Hoffman B. L., Yei S., Wold W. S., Carlin C. Characterization of the adenovirus E3 protein that down-regulates the epidermal growth factor receptor. Evidence for intermolecular disulfide bonding and plasma membrane localization. J Biol Chem. 1992 Jul 5;267(19):13480–13487. [PubMed] [Google Scholar]
  31. Hollenbach P. W., Zilli D. L., Laster S. M. Inhibitors of transcription and translation act synergistically with tumor necrosis factor to cause the activation of phospholipase A2. J Biol Chem. 1992 Jan 5;267(1):39–42. [PubMed] [Google Scholar]
  32. Horton T. M., Ranheim T. S., Aquino L., Kusher D. I., Saha S. K., Ware C. F., Wold W. S., Gooding L. R. Adenovirus E3 14.7K protein functions in the absence of other adenovirus proteins to protect transfected cells from tumor necrosis factor cytolysis. J Virol. 1991 May;65(5):2629–2639. doi: 10.1128/jvi.65.5.2629-2639.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jättelä M., Benedict M., Tewari M., Shayman J. A., Dixit V. M. Bcl-x and Bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholipase A2 in breast carcinoma cells. Oncogene. 1995 Jun 15;10(12):2297–2305. [PubMed] [Google Scholar]
  34. Kenyon D. J., Dougherty J., Raska K., Jr Tumorigenicity of adenovirus-transformed cells and their sensitivity to tumor necrosis factor alpha and NK/LAK cell cytolysis. Virology. 1991 Feb;180(2):818–821. doi: 10.1016/0042-6822(91)90099-w. [DOI] [PubMed] [Google Scholar]
  35. Kirstein M., Baglioni C. Tumor necrosis factor induces synthesis of two proteins in human fibroblasts. J Biol Chem. 1986 Jul 25;261(21):9565–9567. [PubMed] [Google Scholar]
  36. Knauer M. F., Longmuir K. J., Yamamoto R. S., Fitzgerald T. P., Granger G. A. Mechanism of human lymphotoxin and tumor necrosis factor induced destruction of cells in vitro: phospholipase activation and deacylation of specific-membrane phospholipids. J Cell Physiol. 1990 Mar;142(3):469–479. doi: 10.1002/jcp.1041420305. [DOI] [PubMed] [Google Scholar]
  37. Kolesnick R., Golde D. W. The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling. Cell. 1994 May 6;77(3):325–328. doi: 10.1016/0092-8674(94)90147-3. [DOI] [PubMed] [Google Scholar]
  38. Korzeniewski C., Callewaert D. M. An enzyme-release assay for natural cytotoxicity. J Immunol Methods. 1983 Nov 25;64(3):313–320. doi: 10.1016/0022-1759(83)90438-6. [DOI] [PubMed] [Google Scholar]
  39. Krajcsi P., Tollefson A. E., Anderson C. W., Stewart A. R., Carlin C. R., Wold W. S. The E3-10.4K protein of adenovirus is an integral membrane protein that is partially cleaved between Ala22 and Ala23 and has a Ccyt orientation. Virology. 1992 Mar;187(1):131–144. doi: 10.1016/0042-6822(92)90302-6. [DOI] [PubMed] [Google Scholar]
  40. Krajcsi P., Tollefson A. E., Anderson C. W., Wold W. S. The adenovirus E3 14.5-kilodalton protein, which is required for down-regulation of the epidermal growth factor receptor and prevention of tumor necrosis factor cytolysis, is an integral membrane protein oriented with its C terminus in the cytoplasm. J Virol. 1992 Mar;66(3):1665–1673. doi: 10.1128/jvi.66.3.1665-1673.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Kumar S., Baglioni C. Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. J Biol Chem. 1991 Nov 5;266(31):20960–20964. [PubMed] [Google Scholar]
  42. Körner H., Fritzsche U., Burgert H. G. Tumor necrosis factor alpha stimulates expression of adenovirus early region 3 proteins: implications for viral persistence. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11857–11861. doi: 10.1073/pnas.89.24.11857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Laster S. M., Wood J. G., Gooding L. R. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J Immunol. 1988 Oct 15;141(8):2629–2634. [PubMed] [Google Scholar]
  44. Lin L. L., Lin A. Y., DeWitt D. L. Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts. J Biol Chem. 1992 Nov 25;267(33):23451–23454. [PubMed] [Google Scholar]
  45. Lin L. L., Lin A. Y., Knopf J. L. Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6147–6151. doi: 10.1073/pnas.89.13.6147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lin L. L., Wartmann M., Lin A. Y., Knopf J. L., Seth A., Davis R. J. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993 Jan 29;72(2):269–278. doi: 10.1016/0092-8674(93)90666-e. [DOI] [PubMed] [Google Scholar]
  47. Martin S. J., Green D. R. Protease activation during apoptosis: death by a thousand cuts? Cell. 1995 Aug 11;82(3):349–352. doi: 10.1016/0092-8674(95)90422-0. [DOI] [PubMed] [Google Scholar]
  48. Matthews N., Neale M. L., Jackson S. K., Stark J. M. Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism. Immunology. 1987 Sep;62(1):153–155. [PMC free article] [PubMed] [Google Scholar]
  49. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  50. Mutch D. G., Powell C. B., Kao M. S., Collins J. L. Resistance to cytolysis by tumor necrosis factor alpha in malignant gynecological cell lines is associated with the expression of protein(s) that prevent the activation of phospholipase A2 by tumor necrosis factor alpha. Cancer Res. 1992 Feb 15;52(4):866–872. [PubMed] [Google Scholar]
  51. Neale M. L., Fiera R. A., Matthews N. Involvement of phospholipase A2 activation in tumour cell killing by tumour necrosis factor. Immunology. 1988 May;64(1):81–85. [PMC free article] [PubMed] [Google Scholar]
  52. Nemenoff R. A., Winitz S., Qian N. X., Van Putten V., Johnson G. L., Heasley L. E. Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 microtubule-associated protein 2 kinase and protein kinase C. J Biol Chem. 1993 Jan 25;268(3):1960–1964. [PubMed] [Google Scholar]
  53. Opipari A. W., Jr, Hu H. M., Yabkowitz R., Dixit V. M. The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. J Biol Chem. 1992 Jun 25;267(18):12424–12427. [PubMed] [Google Scholar]
  54. Ozaki Y., Ohashi T., Niwa Y. A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function. Inhibitory effects on neutrophil function may not be attributed to inhibition of the lipoxygenase pathway. Biochem Pharmacol. 1986 Oct 15;35(20):3481–3488. doi: 10.1016/0006-2952(86)90615-5. [DOI] [PubMed] [Google Scholar]
  55. Palombella V. J., Vilcek J. Mitogenic and cytotoxic actions of tumor necrosis factor in BALB/c 3T3 cells. Role of phospholipase activation. J Biol Chem. 1989 Oct 25;264(30):18128–18136. [PubMed] [Google Scholar]
  56. Peppelenbosch M. P., Qiu R. G., de Vries-Smits A. M., Tertoolen L. G., de Laat S. W., McCormick F., Hall A., Symons M. H., Bos J. L. Rac mediates growth factor-induced arachidonic acid release. Cell. 1995 Jun 16;81(6):849–856. doi: 10.1016/0092-8674(95)90005-5. [DOI] [PubMed] [Google Scholar]
  57. Prezioso J. A., Wang J., Kim M., Duty L., Tweardy D. J., Gorelik E. Augmentation of TNF cytotoxicity by protein kinase C inhibitors: role of arachidonic acid and manganese superoxide dismutase. Cytokine. 1995 Aug;7(6):517–525. doi: 10.1006/cyto.1995.0070. [DOI] [PubMed] [Google Scholar]
  58. Ranheim T. S., Shisler J., Horton T. M., Wold L. J., Gooding L. R., Wold W. S. Characterization of mutants within the gene for the adenovirus E3 14.7-kilodalton protein which prevents cytolysis by tumor necrosis factor. J Virol. 1993 Apr;67(4):2159–2167. doi: 10.1128/jvi.67.4.2159-2167.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Reid T. R., Torti F. M., Ringold G. M. Evidence for two mechanisms by which tumor necrosis factor kills cells. J Biol Chem. 1989 Mar 15;264(8):4583–4589. [PubMed] [Google Scholar]
  60. Reid T., Ramesha C. S., Ringold G. M. Resistance to killing by tumor necrosis factor in an adipocyte cell line caused by a defect in arachidonic acid biosynthesis. J Biol Chem. 1991 Sep 5;266(25):16580–16586. [PubMed] [Google Scholar]
  61. Rizzo M. T., Boswell H. S., Mangoni L., Carlo-Stella C., Rizzoli V. Arachidonic acid induces c-jun gene expression in stromal cells stimulated by interleukin-1 and tumor necrosis factor-alpha: evidence for a tyrosine-kinase-dependent process. Blood. 1995 Oct 15;86(8):2967–2975. [PubMed] [Google Scholar]
  62. Shisler J., Duerksen-Hughes P., Hermiston T. M., Wold W. S., Gooding L. R. Induction of susceptibility to tumor necrosis factor by E1A is dependent on binding to either p300 or p105-Rb and induction of DNA synthesis. J Virol. 1996 Jan;70(1):68–77. doi: 10.1128/jvi.70.1.68-77.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sparer T. E., Tripp R. A., Dillehay D. L., Hermiston T. W., Wold W. S., Gooding L. R. The role of human adenovirus early region 3 proteins (gp19K, 10.4K, 14.5K, and 14.7K) in a murine pneumonia model. J Virol. 1996 Apr;70(4):2431–2439. doi: 10.1128/jvi.70.4.2431-2439.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stewart A. R., Tollefson A. E., Krajcsi P., Yei S. P., Wold W. S. The adenovirus E3 10.4K and 14.5K proteins, which function to prevent cytolysis by tumor necrosis factor and to down-regulate the epidermal growth factor receptor, are localized in the plasma membrane. J Virol. 1995 Jan;69(1):172–181. doi: 10.1128/jvi.69.1.172-181.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Subramanian T., Boyd J. M., Chinnadurai G. Functional substitution identifies a cell survival promoting domain common to adenovirus E1B 19 kDa and Bcl-2 proteins. Oncogene. 1995 Dec 7;11(11):2403–2409. [PubMed] [Google Scholar]
  66. Suffys P., Beyaert R., De Valck D., Vanhaesebroeck B., Van Roy F., Fiers W. Tumour-necrosis-factor-mediated cytotoxicity is correlated with phospholipase-A2 activity, but not with arachidonic acid release per se. Eur J Biochem. 1991 Jan 30;195(2):465–475. doi: 10.1111/j.1432-1033.1991.tb15727.x. [DOI] [PubMed] [Google Scholar]
  67. Tollefson A. E., Krajcsi P., Pursley M. H., Gooding L. R., Wold W. S. A 14,500 MW protein is coded by region E3 of group C human adenoviruses. Virology. 1990 Mar;175(1):19–29. doi: 10.1016/0042-6822(90)90182-q. [DOI] [PubMed] [Google Scholar]
  68. Tollefson A. E., Krajcsi P., Yei S. P., Carlin C. R., Wold W. S. A 10,400-molecular-weight membrane protein is coded by region E3 of adenovirus. J Virol. 1990 Feb;64(2):794–801. doi: 10.1128/jvi.64.2.794-801.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Tollefson A. E., Stewart A. R., Yei S. P., Saha S. K., Wold W. S. The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus form a complex and function together to down-regulate the epidermal growth factor receptor. J Virol. 1991 Jun;65(6):3095–3105. doi: 10.1128/jvi.65.6.3095-3105.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Tracey K. J., Cerami A. Tumor necrosis factor, other cytokines and disease. Annu Rev Cell Biol. 1993;9:317–343. doi: 10.1146/annurev.cb.09.110193.001533. [DOI] [PubMed] [Google Scholar]
  71. Tsuji Y., Ninomiya-Tsuji J., Torti S. V., Torti F. M. Augmentation by IL-1 alpha of tumor necrosis factor-alpha cytotoxicity in cells transfected with adenovirus E1A. J Immunol. 1993 Mar 1;150(5):1897–1907. [PubMed] [Google Scholar]
  72. Tufariello J. M., Cho S., Horwitz M. S. Adenovirus E3 14.7-kilodalton protein, an antagonist of tumor necrosis factor cytolysis, increases the virulence of vaccinia virus in severe combined immunodeficient mice. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10987–10991. doi: 10.1073/pnas.91.23.10987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Tufariello J., Cho S., Horwitz M. S. The adenovirus E3 14.7-kilodalton protein which inhibits cytolysis by tumor necrosis factor increases the virulence of vaccinia virus in a murine pneumonia model. J Virol. 1994 Jan;68(1):453–462. doi: 10.1128/jvi.68.1.453-462.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Vande Pol S. B., Howley P. M. The bovine papillomavirus constitutive enhancer is essential for viral transformation, DNA replication, and the maintenance of latency. J Virol. 1992 Apr;66(4):2346–2358. doi: 10.1128/jvi.66.4.2346-2358.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Vanhaesebroeck B., Timmers H. T., Pronk G. J., van Roy F., Van der Eb A. J., Fiers W. Modulation of cellular susceptibility to the cytotoxic/cytostatic action of tumor necrosis factor by adenovirus E1 gene expression is cell type-dependent. Virology. 1990 Jun;176(2):362–368. doi: 10.1016/0042-6822(90)90006-d. [DOI] [PubMed] [Google Scholar]
  76. Voelkel-Johnson C., Entingh A. J., Wold W. S., Gooding L. R., Laster S. M. Activation of intracellular proteases is an early event in TNF-induced apoptosis. J Immunol. 1995 Feb 15;154(4):1707–1716. [PubMed] [Google Scholar]
  77. Voelkel-Johnson C., Thorne T. E., Laster S. M. Susceptibility to TNF in the presence of inhibitors of transcription or translation is dependent on the activity of cytosolic phospholipase A2 in human melanoma tumor cells. J Immunol. 1996 Jan 1;156(1):201–207. [PubMed] [Google Scholar]
  78. White E., Blose S. H., Stillman B. W. Nuclear envelope localization of an adenovirus tumor antigen maintains the integrity of cellular DNA. Mol Cell Biol. 1984 Dec;4(12):2865–2875. doi: 10.1128/mcb.4.12.2865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. White E., Sabbatini P., Debbas M., Wold W. S., Kusher D. I., Gooding L. R. The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol. 1992 Jun;12(6):2570–2580. doi: 10.1128/mcb.12.6.2570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Wold W. S. Adenovirus genes that modulate the sensitivity of virus-infected cells to lysis by TNF. J Cell Biochem. 1993 Dec;53(4):329–335. doi: 10.1002/jcb.240530410. [DOI] [PubMed] [Google Scholar]
  81. Wold W. S., Gooding L. R. Adenovirus region E3 proteins that prevent cytolysis by cytotoxic T cells and tumor necrosis factor. Mol Biol Med. 1989 Oct;6(5):433–452. [PubMed] [Google Scholar]
  82. Wold W. S., Gooding L. R. Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology. 1991 Sep;184(1):1–8. doi: 10.1016/0042-6822(91)90815-s. [DOI] [PubMed] [Google Scholar]
  83. Wold W. S., Hermiston T. W., Tollefson A. E. Adenovirus proteins that subvert host defenses. Trends Microbiol. 1994 Nov;2(11):437–443. doi: 10.1016/0966-842x(94)90801-x. [DOI] [PubMed] [Google Scholar]
  84. Wold W. S., Tollefson A. E., Hermiston T. W. E3 transcription unit of adenovirus. Curr Top Microbiol Immunol. 1995;199(Pt 1):237–274. doi: 10.1007/978-3-642-79496-4_13. [DOI] [PubMed] [Google Scholar]
  85. Wong G. H., Elwell J. H., Oberley L. W., Goeddel D. V. Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell. 1989 Sep 8;58(5):923–931. doi: 10.1016/0092-8674(89)90944-6. [DOI] [PubMed] [Google Scholar]
  86. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]
  87. Yang Y. C., Spalholz B. A., Rabson M. S., Howley P. M. Dissociation of transforming and trans-activation functions for bovine papillomavirus type 1. Nature. 1985 Dec 12;318(6046):575–577. doi: 10.1038/318575a0. [DOI] [PubMed] [Google Scholar]
  88. Zilli D., Voelkel-Johnson C., Skinner T., Laster S. M. The adenovirus E3 region 14.7 kDa protein, heat and sodium arsenite inhibit the TNF-induced release of arachidonic acid. Biochem Biophys Res Commun. 1992 Oct 15;188(1):177–183. doi: 10.1016/0006-291x(92)92366-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES