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The Journal of Immunology, 2000, 165: 1074-1081.
Copyright © 2000 by The American Association of Immunologists

Latent Murine {gamma}-Herpesvirus Infection Is Established in Activated B Cells, Dendritic Cells, and Macrophages1

Emilio Flaño2,*,{ddagger}, S. Mazher Husain{dagger},{ddagger}, Jeffery T. Sample{dagger},{ddagger}, David L. Woodland2,*,{ddagger} and Marcia A. Blackman2,3,*,{ddagger}

Departments of * Immunology and {dagger} Virology and Molecular Biology, and {ddagger} Program in Viral Oncogenesis and Tumor Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105; and § Department of Pathology, University of Tennessee, Memphis, TN 38163

Intranasal infection of mice with the murine {gamma}-herpesvirus MHV-68 results in an acute lytic infection in the lung, followed by the establishment of lifelong latency. Development of an infectious mononucleosis-like syndrome correlates with the establishment of latency and is characterized by splenomegaly and the appearance of activated CD8+ T cells in the peripheral blood. Interestingly, a large population of activated CD8+ T cells in the peripheral blood expresses the Vß4+ element in their TCR. In this report we show that MHV-68 latency in the spleen after intranasal infection is harbored in three APC types: B cells, macrophages, and dendritic cells. Surprisingly, since latency has not previously been described in dendritic cells, these cells harbored the highest frequency of latent virus. Among B cells, latency was preferentially associated with activated B cells expressing the phenotype of germinal center B cells, thus formally linking the previously reported association of latency gene expression and germinal centers to germinal center B cells. Germinal center formation, however, was not required for the establishment of latency. Significantly, although three cell types were latently infected, the ability to stimulate Vß4+CD8+ T cell hybridomas was limited to latently infected, activated B cells.




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J. Virol.Home page
S. Marques, S. Efstathiou, K. G. Smith, M. Haury, and J. P. Simas
Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes
J. Virol., July 1, 2003; 77(13): 7308 - 7318.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
I. V. Pavlova, H. W. Virgin IV, and S. H. Speck
Disruption of Gammaherpesvirus 68 Gene 50 Demonstrates that Rta Is Essential for Virus Replication
J. Virol., May 15, 2003; 77(10): 5731 - 5739.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
L. F. van Dyk, H. W. Virgin IV, and S. H. Speck
Maintenance of Gammaherpesvirus Latency Requires Viral Cyclin in the Absence of B Lymphocytes
J. Virol., May 1, 2003; 77(9): 5118 - 5126.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
E. Flano, I.-J. Kim, J. Moore, D. L. Woodland, and M. A. Blackman
Differential {gamma}-Herpesvirus Distribution in Distinct Anatomical Locations and Cell Subsets During Persistent Infection in Mice
J. Immunol., April 1, 2003; 170(7): 3828 - 3834.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. F. Elsawa, W. Taylor, C. C. Petty, I. Marriott, J. V. Weinstock, and K. L. Bost
Reduced CTL Response and Increased Viral Burden in Substance P Receptor-Deficient Mice Infected with Murine {gamma}-Herpesvirus 68
J. Immunol., March 1, 2003; 170(5): 2605 - 2612.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
H. M. Coleman, B. d. Lima, V. Morton, and P. G. Stevenson
Murine Gammaherpesvirus 68 Lacking Thymidine Kinase Shows Severe Attenuation of Lytic Cycle Replication In Vivo but Still Establishes Latency
J. Virol., February 15, 2003; 77(4): 2410 - 2417.
[Abstract] [Full Text] [PDF]


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J. Gen. Virol.Home page
K. Blasdell, C. McCracken, A. Morris, A. A. Nash, M. Begon, M. Bennett, and J. P. Stewart
The wood mouse is a natural host for Murid herpesvirus 4
J. Gen. Virol., January 1, 2003; 84(1): 111 - 113.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
K. K. Jensen, S.-C. Chen, R. W. Hipkin, M. T. Wiekowski, M. A. Schwarz, C.-C. Chou, J. P. Simas, A. Alcami, and S. A. Lira
Disruption of CCL21-Induced Chemotaxis In Vitro and In Vivo by M3, a Chemokine-Binding Protein Encoded by Murine Gammaherpesvirus 68
J. Virol., December 6, 2002; 77(1): 624 - 630.
[Abstract] [Full Text] [PDF]


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JEMHome page
E. Flano, I.-J. Kim, D. L. Woodland, and M. A. Blackman
{gamma}-Herpesvirus Latency Is Preferentially Maintained in Splenic Germinal Center and Memory B Cells
J. Exp. Med., November 18, 2002; 196(10): 1363 - 1372.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
S. Gangappa, S. B. Kapadia, S. H. Speck, and H. W. Virgin IV
Antibody to a Lytic Cycle Viral Protein Decreases Gammaherpesvirus Latency in B-Cell-Deficient Mice
J. Virol., October 17, 2002; 76(22): 11460 - 11468.
[Abstract] [Full Text] [PDF]


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J. Leukoc. Biol.Home page
B. T. Seet and G. McFadden
Viral chemokine-binding proteins
J. Leukoc. Biol., July 1, 2002; 72(1): 24 - 34.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
S. A. Tibbetts, L. F. van Dyk, S. H. Speck, and H. W. Virgin IV
Immune Control of the Number and Reactivation Phenotype of Cells Latently Infected with a Gammaherpesvirus
J. Virol., June 14, 2002; 76(14): 7125 - 7132.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
E. T. Clambey, H. W. Virgin IV, and S. H. Speck
Characterization of a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Gammaherpesvirus 68 Reveals Tissue-Specific Genetic Requirements for Latency
J. Virol., June 5, 2002; 76(13): 6532 - 6544.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
I.-J. Kim, E. Flano, D. L. Woodland, and M. A. Blackman
Antibody-Mediated Control of Persistent {gamma}-Herpesvirus Infection
J. Immunol., April 15, 2002; 168(8): 3958 - 3964.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. Vacheron, S. A. Luther, and H. Acha-Orbea
Preferential Infection of Immature Dendritic Cells and B Cells by Mouse Mammary Tumor Virus
J. Immunol., April 1, 2002; 168(7): 3470 - 3476.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
H. Liu, S. Andreansky, G. Diaz, T. Hogg, and P. C. Doherty
Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of {gamma}-Herpesvirus-Infected CD4-Deficient Mice
J. Immunol., April 1, 2002; 168(7): 3477 - 3483.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
M. A. Jacoby, H. W. Virgin IV, and S. H. Speck
Disruption of the M2 Gene of Murine Gammaherpesvirus 68 Alters Splenic Latency following Intranasal, but Not Intraperitoneal, Inoculation
J. Virol., February 15, 2002; 76(4): 1790 - 1801.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
C. M. Payne, C. J. Heggie, D. G. Brownstein, J. P. Stewart, and J. P. Quinn
Role of Tachykinins in the Host Response to Murine Gammaherpesvirus Infection
J. Virol., November 1, 2001; 75(21): 10467 - 10471.
[Abstract] [Full Text] [PDF]


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JEMHome page
A. Bridgeman, P. G. Stevenson, J. P. Simas, and S. Efstathiou
A Secreted Chemokine Binding Protein Encoded by Murine Gammaherpesvirus-68 Is Necessary for the Establishment of a Normal Latent Load
J. Exp. Med., August 6, 2001; 194(3): 301 - 312.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
H. Adler, M. Messerle, and U. H. Koszinowski
Virus Reconstituted from Infectious Bacterial Artificial Chromosome (BAC)-Cloned Murine Gammaherpesvirus 68 Acquires Wild-Type Properties In Vivo Only after Excision of BAC Vector Sequences
J. Virol., June 15, 2001; 75(12): 5692 - 5696.
[Abstract] [Full Text]


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J. Virol.Home page
R. Rochford, M. L. Lutzke, R. S. Alfinito, A. Clavo, and R. D. Cardin
Kinetics of Murine Gammaherpesvirus 68 Gene Expression following Infection of Murine Cells in Culture and in Mice
J. Virol., June 1, 2001; 75(11): 4955 - 4963.
[Abstract] [Full Text]


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J. Virol.Home page
A. I. Macrae, B. M. Dutia, S. Milligan, D. G. Brownstein, D. J. Allen, J. Mistrikova, A. J. Davison, A. A. Nash, and J. P. Stewart
Analysis of a Novel Strain of Murine Gammaherpesvirus Reveals a Genomic Locus Important for Acute Pathogenesis
J. Virol., June 1, 2001; 75(11): 5315 - 5327.
[Abstract] [Full Text]


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J. Gen. Virol.Home page
M. N. Wakeling, D. J. Roy, A. A. Nash, and J. P. Stewart
Characterization of the murine gammaherpesvirus 68 ORF74 product: a novel oncogenic G protein-coupled receptor
J. Gen. Virol., May 1, 2001; 82(5): 1187 - 1197.
[Abstract] [Full Text]


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JEMHome page
E. J. Usherwood, D. J. Roy, K. Ward, S. L. Surman, B. M. Dutia, M. A. Blackman, J. P. Stewart, and D. L. Woodland
Control of Gammaherpesvirus Latency by Latent Antigen-specific CD8+ T Cells
J. Exp. Med., September 25, 2000; 192(7): 943 - 952.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
S. R. Sarawar, B. J. Lee, S. K. Reiter, and S. P. Schoenberger
Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus
PNAS, May 22, 2001; 98(11): 6325 - 6329.
[Abstract] [Full Text] [PDF]


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JEMHome page
S. Gangappa, L. F. van Dyk, T. J. Jewett, S. H. Speck, and H. W. Virgin IV
Identification of the In Vivo Role of a Viral bcl-2
J. Exp. Med., April 1, 2002; 195(7): 931 - 940.
[Abstract] [Full Text] [PDF]




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