LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis

Journal of Clinical Investigation

Volumn 125, Issue 1, 2015, Pages 304-315

  Ma, Shi Dong ^a   Xu, Xuequn ^a   Plowshay, Julie ^a   Ranheim, Erik A ^a   Burlingham, William J ^b   Jensen, Jeffrey L ^a   Asimakopoulos, Fotis ^a   Tang, Weihua ^c   Gulley, Margaret L ^d   Cesarman, Ethel ^e   Gumperz, Jenny E ^a   Kenney, Shannon C ^a  

^a Department of Oncology ^*  (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^c EAST CAROLINA UNIVERSITY   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^e WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; LATENT MEMBRANE PROTEIN 1; CD40 ANTIGEN; EBV-ASSOCIATED MEMBRANE ANTIGEN, EPSTEIN-BARR VIRUS; MATRIX PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; B CELL LYMPHOMA; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; EPSTEIN BARR VIRUS INFECTION; FETUS; HUMAN; HUMAN CELL; LYMPHOMA; MONONUCLEAR CELL; MOUSE; NONHUMAN; T LYMPHOCYTE; THYMUS; UMBILICAL CORD BLOOD; VIRUS CARCINOGENESIS; VIRUS LATENCY; ANIMAL; CANCER TRANSPLANTATION; CARCINOGENESIS; CELL PROLIFERATION; COMPLICATION; EPSTEIN BARR VIRUS; GENE EXPRESSION; GENE INACTIVATION; GENETICS; IMMUNOLOGY; METABOLISM; NONOBESE DIABETIC MOUSE; PATHOLOGY; SCID MOUSE; SIGNAL TRANSDUCTION; TUMOR CELL CULTURE; VIROLOGY;

ANIMALS; ANTIGENS, CD40; CARCINOGENESIS; CD4-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; EPSTEIN-BARR VIRUS INFECTIONS; GENE EXPRESSION; GENE KNOCKOUT TECHNIQUES; HERPESVIRUS 4, HUMAN; HUMANS; LYMPHOMA; MICE, INBRED NOD; MICE, SCID; NEOPLASM TRANSPLANTATION; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED; VIRAL MATRIX PROTEINS; VIRUS LATENCY;

EID: 84920425517     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI76357     Document Type: Article

References (55)

1. Vereide D, Sugden B. Insights into the evolution of lymphomas induced by Epstein-Barr virus. Adv Cancer Res. 2010;108:1-19.
2. Vereide DT, Sugden B. Lymphomas differ in their dependence on Epstein-Barr virus. Blood. 2011;117(6):1977-1985.
3. Kieff ED, Rickinson AB. Epstein-Barr Virus and its replication. In: Fields BN, Knipe DM, Howley PM, Griffin DE eds. Fields' Virology. 5th ed. Philadelphia, Pennsylvania, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007:2603-2654.
4. Rickinson AB, Kieff ED. Epstein-Barr Virus. In: Fields BN, Knipe DM, Howley PM, Griffin DE eds. Fields' Virology. 5th ed. Philadelphia, Pennsylvania, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007:2655-2700.
5. Rastelli J, et al. LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1. Blood. 2008;111(3):1448-1455.
6. Graham JP, Arcipowski KM, Bishop GA. Differential B-lymphocyte regulation by CD40 and its viral mimic, latent membrane protein 1. Immunol Rev. 2010;237(1):226-248.
7. Kilger E, Kieser A, Baumann M, Hammerschmidt W. Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 1998;17(6):1700-1709.
8. Shair KH, Bendt KM, Edwards RH, Bedford EC, Nielsen JN, Raab-Traub N. EBV latent membrane protein 1 activates Akt, NFκB, and Stat3 in B cell lymphomas. PLoS Pathog. 2007;3(11):e166.
9. Dirmeier U, Neuhierl B, Kilger E, Reisbach G, Sandberg ML, Hammerschmidt W. Latent membrane protein 1 is critical for efficient growth transformation of human B cells by Epstein-Barr virus. Cancer Res. 2003;63(11):2982-2989.
10. Kelly GL, et al. Different patterns of Epstein-Barr virus latency in endemic Burkitt lymphoma (BL) lead to distinct variants within the BL-associated gene expression signature. J Virol. 2013;87(5):2882-2894.
11. Vereide DT, et al. Epstein-Barr virus maintains lymphomas via its miRNAs. Oncogene. 2014;33(10):1258-1264.
12. Giulino L, et al. A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma. Blood. 2011;117(18):4852-4854.
13. Zhang B, et al. Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model. Cell. 2012;148(4):739-751.
14. Brooks JM, Lee SP, Leese AM, Thomas WA, Rowe M, Rickinson AB. Cyclical expression of EBV latent membrane protein 1 in EBV-transformed B cells underpins heterogeneity of epitope presentation and CD8+ T cell recognition. J Immunol. 2009;182(4):1919-1928.
15. Lee DY, Sugden B. The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis. Blood. 2008;111(4):2280-2289.
16. Pratt ZL, Zhang J, Sugden B. The latent membrane protein 1 (LMP1) oncogene of Epstein-Barr virus can simultaneously induce and inhibit apop-tosis in B cells. J Virol. 2012;86(8):4380-4393.
17. Le Clorennec C, et al. Molecular basis of cyto-toxicity of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in EBV latency III B cells: LMP1 induces type II ligand-independent auto-activation of CD95/Fas with caspase 8-mediated apoptosis. J Virol. 2008;82(13):6721-6733.
18. MacArthur GJ, Wilson AD, Birchall MA, Morgan AJ. Primary CD4+ T-cell responses provide both helper and cytotoxic functions during Epstein-Barr virus infection and transformation of fetal cord blood B cells. J Virol. 2007;81(9):4766-4775.
19. Rowe M, Young LS, Crocker J, Stokes H, Henderson S, Rickinson AB. Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the patho-genesis of EBV-positive lymphomas in man. J Exp Med. 1991;173(1):147-158.
20. Clinchy B, Vitetta ES. The use of an anti-CD3 immunotoxin to prevent the development of lymphoproliferative disease in SCID/PBL mice. J Immunol Methods. 1998;218(1-2):141-153.
21. Johannessen I, Asghar M, Crawford DH. Essential role for T cells in human B-cell lym-phoproliferative disease development in severe combined immunodeficient mice. Br J Haematol. 2000;109(3):600-610.
22. Coles RE, Boyle TJ, DiMaio JM, Berend KR, Via DF, Lyerly HK. T cells or active Epstein-Barr virus infection in the development of lymphopro-liferative disease in human B cell-injected severe combined immunodeficient mice. Ann Surg Oncol. 1994;1(5):405-410.
23. Veronese ML, et al. Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. I. T lymphocyte requirement for B cell tumor generation. J Exp Med. 1992;176(6):1763-1767.
24. Chijioke O, et al. Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Rep. 2013;5(6):1489-1498.
25. Cocco M, et al. CD34+ cord blood cell-transplanted Rag2-/-γ(c)-/-mice as a model for Epstein-Barr virus infection. Am J Pathol. 2008;173(5):1369-1378.
26. Ma SD, et al. A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol. 2011;85(1):165-177.
27. Ma SD, et al. An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model. J Virol. 2012;86(15):7976-7987.
28. Strowig T, et al. Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med. 2009;206(6):1423-1434.
29. Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012;12(11):786-798.
30. Rajesh D, et al. Th1 and Th17 immunocompe-tence in humanized NOD/SCID/IL2rγnull mice. Hum Immunol. 2010;71(6):551-559.
31. Prince S, Keating S, Fielding C, Brennan P, Flo-ettmann E, Rowe M. Latent membrane protein 1 inhibits Epstein-Barr virus lytic cycle induction and progress via different mechanisms. J Virol. 2003;77(8):5000-5007.
32. Banerjee S, et al. The EBV Latent Antigen 3C Inhibits Apoptosis through Targeted Regulation of Interferon Regulatory Factors 4 and 8. PLoS Pathog. 2013;9(5):e1003314.
33. Wang L, et al. Oncogenic IRFs provide a survival advantage for Epstein-Barr virus-or human T-cell leukemia virus type 1-transformed cells through induction of BIC expression. J Virol. 2011;85(16):8328-8337.
34. Yang Y, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723-737.
35. Aldinucci D, et al. IRF4 is modulated by CD40L and by apoptotic and anti-proliferative signals in Hodgkin lymphoma. Br J Haematol. 2010;148(1):115-118.
36. Shaffer AL, et al. IRF4 addiction in multiple myeloma. Nature. 2008;454(7201):226-231.
37. Imadome K, Shirakata M, Shimizu N, Nonoyama S, Yamanashi Y. CD40 ligand is a critical effector of Epstein-Barr virus in host cell survival and transformation. Proc Natl Acad Sci U S A. 2003;100(13):7836-7840.
38. Lowe M, et al. A novel monoclonal antibody to CD40 prolongs islet allograft survival. Am J Transplant. 2012;12(8):2079-2087.
39. Ferran C, Bach JF, Chatenoud L. In vivo T cell activation properties of anti-T cell monoclonal antibodies. Exp Nephrol. 1993;1(2):83-89.
40. Ellenhorn JD, Woodle ES, Ghobreal I, Thistle-thwaite JR, Bluestone JA. Activation of human T cells in vivo following treatment of transplant recipients with OKT3. Transplantation. 1990;50(4):608-612.
41. Pittaluga S, Jaffe ES. T-cell/histiocyte-rich large B-cell lymphoma. Haematologica. 2010;95(3):352-356.
42. Haas A, Zimmermann K, Oxenius A. Antigen-dependent and-independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection. J Virol. 2011;85(23):12102-12113.
43. Epeldegui M, Thapa DR, De la Cruz J, Kitchen S, Zack JA, Martinez-Maza O. CD40 ligand (CD154) incorporated into HIV virions induces activation-induced cytidine deaminase (AID) expression in human B lymphocytes. PLoS One. 2010;5(7):e11448.
44. Boneparth A, Davidson A. B-cell activating factor targeted therapy and lupus. Arthritis Res Ther. 2012;14(suppl 4):S2.
45. Schmidt MR, Appel MC, Giassi LJ, Greiner DL, Shultz LD, Woodland RT. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice. PLoS One. 2008;3(9):e3192.
46. He B, Raab-Traub N, Casali P, Cerutti A. EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. J Immunol. 2003;171(10):5215-5224.
47. Kis LL, et al. In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2. Int J Cancer. 2005;113(6):937-945.
48. Portis T, Longnecker R. Epstein-Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/Akt pathway. Oncogene. 2004;23(53):8619-8628.
49. Skalska L, White RE, Parker GA, Sinclair AJ, Paschos K, Allday MJ. Induction of p16(INK4a) is the major barrier to proliferation when Epstein-Barr virus (EBV) transforms primary B cells into lymphoblastoid cell lines. PLoS Pathog. 2013;9(2):e1003187.
50. Wilson AD, Morgan AJ. Primary immune responses by cord blood CD4(+) T cells and NK cells inhibit Epstein-Barr virus B-cell transformation in vitro. J Virol. 2002;76(10):5071-5081.
51. Yao S, Zhu Y, Chen L. Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov. 2013;12(2):130-146.
52. Kasran A, et al. Safety and tolerability of antagonist anti-human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease. Aliment Pharmacol Ther. 2005;22(2):111-122.
53. Fanale M, et al. Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma. Br J Haematol. 2014;164(2):258-265.
54. Delecluse HJ, Hilsendegen T, Pich D, Zeidler R, Hammerschmidt W. Propagation and recovery of intact, infectious Epstein-Barr virus from pro-karyotic to human cells. Proc Natl Acad Sci U S A. 1998;95(14):8245-8250.
55. Ryan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N, Gulley ML. Epstein-Barr virus quantita-tion by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn. 2004;6(4):378-385.