期刊论文详细信息
Retrovirology
B cell lymphoma in hiv transgenic mice
Joseph Bryant4  Robert C Gallo1  Davide Zella3  Alfredo Garzino-Demo2  Mark K Lafferty2  Yanto Lunardi-Iskandar4  Marvin Reitz4  Selvi Krishnan4  Sabrina Curreli4 
[1] Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
关键词: Transgenic mice;    HIV-1;    B lymphoma;   
Others  :  1209068
DOI  :  10.1186/1742-4690-10-92
 received in 2013-06-04, accepted in 2013-08-22,  发布年份 2013
PDF
【 摘 要 】

Background

Human Immunodeficiency Virus Type I (HIV-1) infection is associated with a high incidence of B-cell lymphomas. The role of HIV in these lymphomas is unclear and currently there are no valid in vivo models for better understanding HIV-related lymphomagenesis. Transgenic (Tg) 26 mice have a 7.4-kb pNL4-3 HIV-1 provirus lacking a 3.1-kb sequence encompassing parts of the gag-pol region. Approximately 15% of these HIV Tg mice spontaneously develop lymphoma with hallmark pre-diagnostic markers including skin lesions, diffuse lymphadenopathy and an increase in pro-inflammatory serum cytokines. Here we describe the phenotypic and molecular characteristics of the B cell leukemia/lymphoma in the Tg mice.

Results

The transformed B cell population consists of CD19+pre-BCR+CD127+CD43+CD93+ precursor B cells. The tumor cells are clonal and characterized by an increased expression of several cellular oncogenes. Expression of B cell-stimulatory cytokines IL-1β, IL-6, IL-10, IL-12p40, IL-13 and TNFα and HIV proteins p17, gp120 and nef were elevated in the Tg mice with lymphoma.

Conclusions

Increased expression of HIV proteins and the B-cell stimulatory factors is consistent with the interpretation that one or more of these factors play a role in lymphoma development. The lymphomas share many similarities with those occurring in HIV/AIDS+ patients and may provide a valuable model for understanding AIDS-related lymphomagenesis and elucidating the role played by HIV-1.

【 授权许可】

   
2013 Curreli et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150602081138264.pdf 1637KB PDF download
Figure 5. 80KB Image download
Figure 4. 80KB Image download
Figure 3. 83KB Image download
Figure 2. 66KB Image download
Figure 1. 132KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Grogg KL, Miller RF, Dogan A: HIV infection and lymphoma. J Clin Pathol 2007, 60:1365-1372.
  • [2]Besson C, Goubar A, Gabarre J, Rozenbaum W, Pialoux G, Chatelet FP, Katlama C, Charlotte F, Dupont B, Brousse N, et al.: Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood 2001, 98:2339-2344.
  • [3]Epeldegui M, Widney DP, Martinez-Maza O: Pathogenesis of AIDS lymphoma: role of oncogenic viruses and B cell activation-associated molecular lesions. Curr Opin Oncol 2006, 18:444-448.
  • [4]Pelicci PG, Knowles DM 2nd, Arlin ZA, Wieczorek R, Luciw P, Dina D, Basilico C, Dalla-Favera R: Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. J Exp Med 1986, 164:2049-2060.
  • [5]Przybylski GK, Goldman J, Ng VL, McGrath MS, Herndier BG, Schenkein DP, Monroe JG, Silberstein LE: Evidence for early B-cell activation preceding the development of Epstein-Barr virus-negative acquired immunodeficiency syndrome-related lymphoma. Blood 1996, 88:4620-4629.
  • [6]Martinez-Maza O, Breen EC: B-cell activation and lymphoma in patients with HIV. Curr Opin Oncol 2002, 14:528-532.
  • [7]Vendrame E, Martinez-Maza O: Assessment of pre-diagnosis biomarkers of immune activation and inflammation: insights on the etiology of lymphoma. J Proteome Res 2011, 10:113-119.
  • [8]Widney D, Gundapp G, Said JW, van der Meijden M, Bonavida B, Demidem A, Trevisan C, Taylor J, Detels R, Martinez-Maza O: Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma. Clin Immunol 1999, 93:114-123.
  • [9]Breen EC, Fatahi S, Epeldegui M, Boscardin WJ, Detels R, Martinez-Maza O: Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma. Tumour Biol 2006, 27:187-194.
  • [10]He B, Qiao X, Klasse PJ, Chiu A, Chadburn A, Knowles DM, Moore JP, Cerutti A: HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors. J Immunol 2006, 176:3931-3941.
  • [11]Lefevre EA, Krzysiek R, Loret EP, Galanaud P, Richard Y: Cutting edge: HIV-1 Tat protein differentially modulates the B cell response of naive, memory, and germinal center B cells. J Immunol 1999, 163:1119-1122.
  • [12]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:e11448.
  • [13]van Baarle D, Hovenkamp E, Callan MF, Wolthers KC, Kostense S, Tan LC, Niesters HG, Osterhaus AD, McMichael AJ, van Oers MH, Miedema F: Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma. Blood 2001, 98:146-155.
  • [14]Carbone A, Gloghini A: KSHV/HHV8-associated lymphomas. Br J Haematol 2008, 140:13-24.
  • [15]Leonard JM, Abramczuk JW, Pezen DS, Rutledge R, Belcher JH, Hakim F, Shearer G, Lamperth L, Travis W, Fredrickson T, et al.: Development of disease and virus recovery in transgenic mice containing HIV proviral DNA. Science 1988, 242:1665-1670.
  • [16]Feinberg MB, Moore JP: AIDS vaccine models: challenging challenge viruses. Nat Med 2002, 8:207-210.
  • [17]Tinkle BT, Ueda H, Ngo L, Luciw PA, Shaw K, Rosen CA, Jay G: Transgenic dissection of HIV genes involved in lymphoid depletion. J Clin Invest 1997, 100:32-39.
  • [18]Hanna Z, Kay DG, Cool M, Jothy S, Rebai N, Jolicoeur P: Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease. J Virol 1998, 72:121-132.
  • [19]van Maanen M, Sutton RE: Rodent models for HIV-1 infection and disease. Current HIV research 2003, 1:121-130.
  • [20]Dickie P, Felser J, Eckhaus M, Bryant J, Silver J, Marinos N, Notkins AL: HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. Virology 1991, 185:109-119.
  • [21]Kopp JB, Klotman ME, Adler SH, Bruggeman LA, Dickie P, Marinos NJ, Eckhaus M, Bryant JL, Notkins AL, Klotman PE: Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci USA 1992, 89:1577-1581.
  • [22]Kopp JB, Rooney JF, Wohlenberg C, Dorfman N, Marinos NJ, Bryant JL, Katz SI, Notkins AL, Klotman PE: Cutaneous disorders and viral gene expression in HIV-1 transgenic mice. AIDS Res Hum Retroviruses 1993, 9:267-275.
  • [23]Santoro TJ, Bryant JL, Pellicoro J, Klotman ME, Kopp JB, Bruggeman LA, Franks RR, Notkins AL, Klotman PE: Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice. Virology 1994, 201:147-151.
  • [24]Stoltzfus CM: Regulation of HIV-1 alternative RNA splicing and its role in virus replication. Adv Virus Res 2009, 74:1-40.
  • [25]Giagulli C, Marsico S, Magiera AK, Bruno R, Caccuri F, Barone I, Fiorentini S, Ando S, Caruso A: Opposite effects of HIV-1 p17 variants on PTEN activation and cell growth in B cells. PLoS One 2011, 6:e17831.
  • [26]Swingler S, Brichacek B, Jacque JM, Ulich C, Zhou J, Stevenson M: HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature 2003, 424:213-219.
  • [27]Breen EC, Boscardin WJ, Detels R, Jacobson LP, Smith MW, O'Brien SJ, Chmiel JS, Rinaldo CR, Lai S, Martinez-Maza O: Non-Hodgkin's B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the IL10 promoter −592 C/C genotype. Clin Immunol 2003, 109:119-129.
  • [28]Purdue MP, Lan Q, Bagni R, Hocking WG, Baris D, Reding DJ, Rothman N: Prediagnostic serum levels of cytokines and other immune markers and risk of non-hodgkin lymphoma. Cancer Res 2011, 71:4898-4907.
  • [29]Hardy RR, Hayakawa K: B cell development pathways. Annu Rev Immunol 2001, 19:595-621.
  • [30]Kawamoto H, Ikawa T, Ohmura K, Fujimoto S, Katsura Y: T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver. Immunity 2000, 12:441-450.
  • [31]Rui L, Schmitz R, Ceribelli M, Staudt LM: Malignant pirates of the immune system. Nat Immunol 2011, 12:933-940.
  • [32]Klapproth K, Wirth T: Advances in the understanding of MYC-induced lymphomagenesis. Br J Haematol 2010, 149:484-497.
  • [33]Polo JM, Juszczynski P, Monti S, Cerchietti L, Ye K, Greally JM, Shipp M, Melnick A: Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci USA 2007, 104:3207-3212.
  • [34]Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, et al.: Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci USA 2012, 109:3879-3884.
  • [35]Rosenberg N, Witte ON: The viral and cellular forms of the Abelson (abl) oncogene. Adv Virus Res 1988, 35:39-81.
  • [36]Shore SK, Tantravahi RV, Reddy EP: Transforming pathways activated by the v-Abl tyrosine kinase. Oncogene 2002, 21:8568-8576.
  • [37]Hartley JW, Evans LH, Green KY, Naghashfar Z, Macias AR, Zerfas PM, Ward JM: Expression of infectious murine leukemia viruses by RAW264.7 cells, a potential complication for studies with a widely used mouse macrophage cell line. Retrovirology 2008, 5:1. BioMed Central Full Text
  • [38]Popovic M: Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy. Proc Natl Acad Sci USA 1995, 102(41):14807-14812.
  • [39]Allman D, Lindsley RC, DeMuth W, Rudd K, Shinton SA, Hardy RR: Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation. J Immunol 2001, 167:6834-6840.
  • [40]Kondo M, Weissman IL, Akashi K: Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997, 91(5):661-672.
  • [41]Herzog S, Reth M, Jumaa H: Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nat Rev Immunol 2009, 9:195-205.
  • [42]Ochiai K, Maienschein-Cline M, Mandal M, Triggs JR, Bertolino E, Sciammas R, Dinner AR, Clark MR, Singh H: A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation. Nat Immunol 2012, 13:300-307.
  • [43]Perez-Vera P, Reyes-Leon A, Fuentes-Panana EM: Signaling proteins and transcription factors in normal and malignant early B cell development. Bone Marrow Res 2011, 2011:502751.
  • [44]Deffenbacher KE, Iqbal J, Liu Z, Fu K, Chan WC: Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: an integrated analysis of DNA copy number and gene expression. J Acquir Immune Defic Syndr 2010, 54:18-26.
  • [45]Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403:503-511.
  • [46]Teitell MA, Pandolfi PP: Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol 2009, 4:175-198.
  • [47]Ballerini P, Gaidano G, Gong JZ, Tassi V, Saglio G, Knowles DM, Dalla-Favera R: Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Blood 1993, 81:166-176.
  • [48]Grulich AE, Wan X, Law MG, Milliken ST, Lewis CR, Garsia RJ, Gold J, Finlayson RJ, Cooper DA, Kaldor JM: B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS. AIDS 2000, 14:133-140.
  • [49]Kozak CA: The mouse "xenotropic" gammaretroviruses and their XPR1 receptor. Retrovirology 2010, 7:101. BioMed Central Full Text
  • [50]Wong R, Balachandran A, Mao AY, Dobson W, Gray-Owen S, Cochrane A: Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy. Retrovirology 2011, 8:47. BioMed Central Full Text
  文献评价指标  
  下载次数:21次 浏览次数:6次