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PMID: 12438427 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells.

The Journal of experimental medicine ·Vol. 196 ·No. 10 ·2002-11-18 ·Pages 1363-72

Flaño E, Kim IJ, Woodland DL, Blackman MA

Abstract

The gamma-herpesviruses are oncogenic B cell lymphotrophic viruses that establish life-long latency in the host. Murine gamma-herpesvirus 68 (MHV-68) infection of mice represents a unique system for analyzing gamma-herpesvirus latency in splenic B cells at different stages of infection. After intranasal infection with MHV-68 we analyzed the establishment of latency 14 days after infection, and the maintenance of latency 3 months after infection in different purified subpopulations of B cells in the spleen. The data show that MHV-68 latency is mainly established in germinal center B cells and that long-term latency is preferentially maintained in two different subsets of isotype-switched B cells, germinal center and memory B cells. Cell cycle analysis indicates that MHV-68 is located in both cycling and resting isotype-switched B cells. Analysis of viral gene expression showed that both lytic and latent viral transcripts were differentially expressed in germinal center and memory B cells during long-term latency. Together, these observations suggested that gamma-herpesviruses exploit the B cell life cycle in the spleen.

MeSH Terms
Animals B-Lymphocytes/immunology,virology Cell Cycle Flow Cytometry Gene Expression Profiling Herpesviridae/physiology Immunologic Memory Mice Polymerase Chain Reaction Spleen/virology Virus Latency
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Flaño Emilio
Trudeau Institute, Saranac Lake, NY 12983, USA.
Kim In-Jeong
Woodland David L
Blackman Marcia A
References (68)
68 references, click to expand
  1. Characterization of the murine gammaherpesvirus 68 ORF74 product: a novel oncogenic G protein-coupled receptor.
    J Gen Virol. 2001 May;82(Pt 5):1187-97 PMID: 11297694
  2. Natural history of murine gamma-herpesvirus infection.
    Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29;356(1408):569-79 PMID: 11313012
  3. Dissecting the host response to a gamma-herpesvirus.
    Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29;356(1408):581-93 PMID: 11313013
  4. Cutting edge: cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein protects germinal center B cells from apoptosis during germinal center reactions.
    J Immunol. 2001 Jun 1;166(11):6473-6 PMID: 11359796
  5. Unraveling immunity to gamma-herpesviruses: a new model for understanding the role of immunity in chronic virus infection.
    Curr Opin Immunol. 1999 Aug;11(4):371-9 PMID: 10448140
  6. Requirement for CD4+ T cells in V beta 4+CD8+ T cell activation associated with latent murine gammaherpesvirus infection.
    J Immunol. 1999 Sep 15;163(6):3403-8 PMID: 10477611
  7. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses.
    Science. 1999 Oct 8;286(5438):300-3 PMID: 10514374
  8. A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells.
    Life Sci. 1999;65(14):1433-53 PMID: 10530796
  9. Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action.
    J Virol. 2000 Aug;74(15):6741-7 PMID: 10888612
  10. Murine gammaherpesvirus 68 cyclin D homologue is required for efficient reactivation from latency.
    J Virol. 2000 Aug;74(15):7016-23 PMID: 10888640
  11. Inhibition of MHC class I-restricted antigen presentation by gamma 2-herpesviruses.
    Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8455-60 PMID: 10890918
  12. Analysis of virus-specific CD4(+) t cells during long-term gammaherpesvirus infection.
    J Virol. 2001 Aug;75(16):7744-8 PMID: 11462049
  13. Function of Rta is essential for lytic replication of murine gammaherpesvirus 68.
    J Virol. 2001 Oct;75(19):9262-73 PMID: 11533188
  14. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow.
    J Exp Med. 2001 Oct 15;194(8):1151-64 PMID: 11602643
  15. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation.
    J Virol. 2002 Feb;76(4):1790-801 PMID: 11799175
  16. Physical association of the K3 protein of gamma-2 herpesvirus 68 with major histocompatibility complex class I molecules with impaired peptide and beta(2)-microglobulin assembly.
    J Virol. 2002 Mar;76(6):2796-803 PMID: 11861847
  17. Epstein-Barr virus: exploiting the immune system.
    Nat Rev Immunol. 2001 Oct;1(1):75-82 PMID: 11905817
  18. Identification of the in vivo role of a viral bcl-2.
    J Exp Med. 2002 Apr 1;195(7):931-40 PMID: 11927636
  19. Antibody-mediated control of persistent gamma-herpesvirus infection.
    J Immunol. 2002 Apr 15;168(8):3958-64 PMID: 11937552
  20. A mouse model for infectious mononucleosis.
    Immunol Res. 2002;25(3):201-17 PMID: 12018460
  21. The dispersal of mucosal memory B cells: evidence from persistent EBV infection.
    Immunity. 2002 May;16(5):745-54 PMID: 12049725
  22. The relationship between surface immunoglobulin isotype and the immune function of murine B lymphocytes. V. High affinity secondary antibody responses are transferred by both IgD-positive and IgD-negative memory B cells.
    J Immunol. 1981 Sep;127(3):867-72 PMID: 6167629
  23. A pragmatic approach to the analysis of DNA histograms with a definable G1 peak.
    Cytometry. 1987 Jan;8(1):1-8 PMID: 3803091
  24. Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes.
    J Virol. 1992 Jun;66(6):3715-24 PMID: 1316478
  25. Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo.
    J Gen Virol. 1992 Dec;73 ( Pt 12):3275-9 PMID: 1469366
  26. Interactions of murine gammaherpesvirus 68 with B and T cell lines.
    Virology. 1993 Apr;193(2):825-33 PMID: 8460488
  27. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state.
    J Virol. 1994 Nov;68(11):7374-85 PMID: 7933121
  28. Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation.
    J Exp Med. 1996 May 1;183(5):2303-12 PMID: 8642339
  29. CD28 is required for germinal center formation.
    J Immunol. 1996 Jun 15;156(12):4576-81 PMID: 8648099
  30. Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice.
    Nature. 1996 Aug 1;382(6590):462-6 PMID: 8684487
  31. Characterization of tumor cell lines derived from murine gammaherpesvirus-68-infected mice.
    J Virol. 1996 Sep;70(9):6516-8 PMID: 8709292
  32. Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68.
    J Virol. 1996 Oct;70(10):6775-80 PMID: 8794315
  33. Mouse CD38 is down-regulated on germinal center B cells and mature plasma cells.
    J Immunol. 1997 Feb 1;158(3):1108-15 PMID: 9013949
  34. Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells.
    J Exp Med. 1996 Sep 1;184(3):863-71 PMID: 9064346
  35. Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell.
    J Virol. 1997 Jul;71(7):4882-91 PMID: 9188550
  36. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients.
    Science. 1997 Jun 20;276(5320):1851-4 PMID: 9188529
  37. Complete sequence and genomic analysis of murine gammaherpesvirus 68.
    J Virol. 1997 Aug;71(8):5894-904 PMID: 9223479
  38. Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus-induced vascular disease.
    Nat Med. 1997 Dec;3(12):1346-53 PMID: 9396604
  39. Kinetics of establishing the memory B cell population as revealed by CD38 expression.
    J Immunol. 1998 May 15;160(10):4688-95 PMID: 9590214
  40. Lung epithelial cells are a major site of murine gammaherpesvirus persistence.
    J Exp Med. 1998 Jun 15;187(12):1941-51 PMID: 9625754
  41. EBV persistence in memory B cells in vivo.
    Immunity. 1998 Sep;9(3):395-404 PMID: 9768759
  42. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells.
    J Exp Med. 1998 Nov 2;188(9):1679-89 PMID: 9802980
  43. Non-antigen-specific B-cell activation following murine gammaherpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo.
    J Virol. 1999 Feb;73(2):1075-9 PMID: 9882308
  44. Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection.
    J Gen Virol. 1999 Jan;80 ( Pt 1):75-82 PMID: 9934687
  45. Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice.
    J Virol. 1999 Mar;73(3):2321-32 PMID: 9971815
  46. Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells.
    J Virol. 1999 Apr;73(4):3273-83 PMID: 10074181
  47. Identification and initial characterization of the murine gammaherpesvirus 68 gene M3, encoding an abundantly secreted protein.
    J Virol. 1999 May;73(5):4524-9 PMID: 10196360
  48. B cells regulate murine gammaherpesvirus 68 latency.
    J Virol. 1999 Jun;73(6):4651-61 PMID: 10233924
  49. The murine gammaherpesvirus 68 v-cyclin gene is an oncogene that promotes cell cycle progression in primary lymphocytes.
    J Virol. 1999 Jun;73(6):5110-22 PMID: 10233974
  50. Murine gammaherpesvirus M2 gene is latency-associated and its protein a target for CD8(+) T lymphocytes.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7508-13 PMID: 10377445
  51. Consideration of host-viral interactions in the pathogenesis of Kaposi's sarcoma.
    J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S58-65 PMID: 10430220
  52. The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF-induced apoptosis.
    J Gen Virol. 1999 Oct;80 ( Pt 10):2737-40 PMID: 10573168
  53. Disruption of the murine gammaherpesvirus 68 M1 open reading frame leads to enhanced reactivation from latency.
    J Virol. 2000 Feb;74(4):1973-84 PMID: 10644370
  54. Characterization of gammaherpesvirus 68 gene 50 transcription.
    J Virol. 2000 Feb;74(4):2029-37 PMID: 10644377
  55. A broad spectrum secreted chemokine binding protein encoded by a herpesvirus.
    J Exp Med. 2000 Feb 7;191(3):573-8 PMID: 10662803
  56. Epstein-Barr virus: Co-opting B-cell memory and migration.
    Curr Biol. 2000 Feb 10;10(3):R120-3 PMID: 10679312
  57. Rta of murine gammaherpesvirus 68 reactivates the complete lytic cycle from latency.
    J Virol. 2000 Apr;74(8):3659-67 PMID: 10729142
  58. Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages.
    J Immunol. 2000 Jul 15;165(2):1074-81 PMID: 10878386
  59. The murine gammaherpesvirus 68 v-cyclin is a critical regulator of reactivation from latency.
    J Virol. 2000 Aug;74(16):7451-61 PMID: 10906198
  60. EBV persistence involves strict selection of latently infected B cells.
    J Immunol. 2000 Sep 15;165(6):2975-81 PMID: 10975805
  61. Control of gammaherpesvirus latency by latent antigen-specific CD8(+) T cells.
    J Exp Med. 2000 Oct 2;192(7):943-52 PMID: 11015436
  62. Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils.
    J Virol. 2000 Nov;74(21):9964-71 PMID: 11024124
  63. Tonsillar memory B cells, latently infected with Epstein-Barr virus, express the restricted pattern of latent genes previously found only in Epstein-Barr virus-associated tumors.
    Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12250-5 PMID: 11035774
  64. Murine gamma-herpesvirus-68: a mouse model for infectious mononucleosis?
    Mol Med Today. 2000 Dec;6(12):488-90 PMID: 11099955
  65. EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency.
    Immunity. 2000 Oct;13(4):485-95 PMID: 11070167
  66. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell.
    Immunity. 2000 Oct;13(4):497-506 PMID: 11070168
  67. Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire.
    Immunity. 2001 Feb;14(2):181-92 PMID: 11239450
  68. Virus-specific and bystander CD8+ T-cell proliferation in the acute and persistent phases of a gammaherpesvirus infection.
    J Virol. 2001 May;75(9):4435-8 PMID: 11287596
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2002-11-18
Pages
1363-72
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193987
Subset
IM
Grants
NIAID NIH HHS · R01 AI042927 · United States
NIAID NIH HHS · AI42927 · United States
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