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 resul ts in an acute lytic infection in the lung, followed by the establishment o f lifelong latency. Development of an infectious mononucleosis-like syndrom e correlates with the establishment of latency and is characterized by sple nomegaly and the appearance of activated CD8(+) T cells in the peripheral b lood. Interestingly, a large population of activated CD8(+) T cells in the peripheral blood expresses the V beta 4(+) element in their TCR, In this re port we show that MHV-68 latency in the spleen after intranasal infection i s harbored in three APC types: B cells, macrophages, and dendritic cells. S urprisingly, since latency has not previously been described in dendritic c ells, these cells harbored the highest frequency of latent virus. Among B c ells, latency was preferentially associated with activated B cells expressi ng the phenotype of germinal center B cells, thus formally linking the prev iously reported association of latency gene expression and germinal centers to germinal center B cells. Germinal center formation, however, was not re quired for the establishment of latency. Significantly, although three cell types were latently infected, the ability to stimulate V beta b4(+)CD8(+) T cell hybridomas was limited to latently infected, activated B cells.