Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages.
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 V beta 4+ 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 V beta 4+CD8+ T cell hybridomas was limited to latently infected, activated B cells.
Flaño
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E
Department of Immunology, Program in Viral Oncogenesis and Tumor Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Husain
S M
SM
Sample
J T
JT
Woodland
D L
DL
Blackman
M A
MA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D018142:Gammaherpesvirinae / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000821:virology; D006825:Hybridomas; D007244:Infectious Mononucleosis / Q000276:immunology / Q000821:virology; D008024:Ligands; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta