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-Herpesvirus Infection Is Established in Activated B Cells, Dendritic Cells, and Macrophages1
,,,§,§,§
Departments of
*
Immunology and
Virology and Molecular Biology, and
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 
-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. J. Obar, S. G. Crist, E. K. Leung, and E. J. Usherwood IL-15-Independent Proliferative Renewal of Memory CD8+ T Cells in Latent Gammaherpesvirus Infection J. Immunol., August 15, 2004; 173(4): 2705 - 2714. [Abstract] [Full Text] [PDF]
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R. L. Sparks-Thissen, D. C. Braaten, S. Kreher, S. H. Speck, and H. W. Virgin IV An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection J. Virol., July 1, 2004; 78(13): 6827 - 6835. [Abstract] [Full Text] [PDF]
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J. S. McClellan, S. A. Tibbetts, S. Gangappa, K. A. Brett, and H. W. Virgin IV Critical Role of CD4 T Cells in an Antibody-Independent Mechanism of Vaccination against Gammaherpesvirus Latency J. Virol., July 1, 2004; 78(13): 6836 - 6845. [Abstract] [Full Text] [PDF]
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B. M. Dutia, D. J. Roy, B. Ebrahimi, B. Gangadharan, S. Efstathiou, J. P. Stewart, and A. A. Nash Identification of a region of the virus genome involved in murine gammaherpesvirus 68-induced splenic pathology J. Gen. Virol., June 1, 2004; 85(6): 1393 - 1400. [Abstract] [Full Text] [PDF]
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D. Verzijl, C. P. Fitzsimons, M. van Dijk, J. P. Stewart, H. Timmerman, M. J. Smit, and R. Leurs Differential Activation of Murine Herpesvirus 68- and Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF74 G Protein-Coupled Receptors by Human and Murine Chemokines J. Virol., April 1, 2004; 78(7): 3343 - 3351. [Abstract] [Full Text] [PDF]
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E. Flano, C. L. Hardy, I.-J. Kim, C. Frankling, M. A. Coppola, P. Nguyen, D. L. Woodland, and M. A. Blackman T Cell Reactivity during Infectious Mononucleosis and Persistent Gammaherpesvirus Infection in Mice J. Immunol., March 1, 2004; 172(5): 3078 - 3085. [Abstract] [Full Text] [PDF]
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A. C. Townsley, B. M. Dutia, and A. A. Nash The M4 Gene of Murine Gammaherpesvirus Modulates Productive and Latent Infection In Vivo J. Virol., January 15, 2004; 78(2): 758 - 767. [Abstract] [Full Text] [PDF]
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J. J. Obar, S. G. Crist, D. C. Gondek, and E. J. Usherwood Different Functional Capacities of Latent and Lytic Antigen-Specific CD8 T Cells in Murine Gammaherpesvirus Infection J. Immunol., January 15, 2004; 172(2): 1213 - 1219. [Abstract] [Full Text] [PDF]
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J. S. May, H. M. Coleman, B. Smillie, S. Efstathiou, and P. G. Stevenson Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68 J. Gen. Virol., January 1, 2004; 85(1): 137 - 146. [Abstract] [Full Text] [PDF]
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S. F. Elsawa and K. L. Bost Murine {gamma}-Herpesvirus-68-Induced IL-12 Contributes to the Control of Latent Viral Burden, but Also Contributes to Viral-Mediated Leukocytosis J. Immunol., January 1, 2004; 172(1): 516 - 524. [Abstract] [Full Text] [PDF]
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E. Bortz, J. P. Whitelegge, Q. Jia, Z. H. Zhou, J. P. Stewart, T.-T. Wu, and R. Sun Identification of Proteins Associated with Murine Gammaherpesvirus 68 Virions J. Virol., December 15, 2003; 77(24): 13425 - 13432. [Abstract] [Full Text] [PDF]
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P. Fowler, S. Marques, J. P. Simas, and S. Efstathiou ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency J. Gen. Virol., December 1, 2003; 84(12): 3405 - 3416. [Abstract] [Full Text] [PDF]
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N. J. Moorman, D. O. Willer, and S. H. Speck The Gammaherpesvirus 68 Latency-Associated Nuclear Antigen Homolog Is Critical for the Establishment of Splenic Latency J. Virol., October 1, 2003; 77(19): 10295 - 10303. [Abstract] [Full Text] [PDF]
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D. Martinez-Guzman, T. Rickabaugh, T.-T. Wu, H. Brown, S. Cole, M. J. Song, L. Tong, and R. Sun Transcription Program of Murine Gammaherpesvirus 68 J. Virol., October 1, 2003; 77(19): 10488 - 10503. [Abstract] [Full Text] [PDF]
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A. I. Macrae, E. J. Usherwood, S. M. Husain, E. Flano, I.-J. Kim, D. L. Woodland, A. A. Nash, M. A. Blackman, J. T. Sample, and J. P. Stewart Murid Herpesvirus 4 Strain 68 M2 Protein Is a B-Cell-Associated Antigen Important for Latency but Not Lymphocytosis J. Virol., September 1, 2003; 77(17): 9700 - 9709. [Abstract] [Full Text] [PDF]
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D. O. Willer and S. H. Speck Long-Term Latent Murine Gammaherpesvirus 68 Infection Is Preferentially Found within the Surface Immunoglobulin D-Negative Subset of Splenic B Cells In Vivo J. Virol., August 1, 2003; 77(15): 8310 - 8321. [Abstract] [Full Text] [PDF]
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I.-J. Kim, E. Flano, D. L. Woodland, F. E. Lund, T. D. Randall, and M. A. Blackman Maintenance of Long Term {gamma}-Herpesvirus B Cell Latency Is Dependent on CD40-Mediated Development of Memory B Cells J. Immunol., July 15, 2003; 171(2): 886 - 892. [Abstract] [Full Text] [PDF]
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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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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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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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