title: Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells.
abstract: Kaposi sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic virus whose primary site of replication is the oropharynx. KSHV can infect both T and B cells from primary tonsillar explant cultures. However, T cells do not support lytic replication, while B cells spontaneously produce substantial amounts of infectious virus. Here, we provide evidence for a mechanism by which activated T cells may promote or stabilize latency of KSHV infection in B cells. When mixed cultures of B cells and activated T cells were exposed to KSHV, little spontaneous virus production was observed. Removing T cells from the mix or treating the mixed culture with immune suppressants enhanced virus production. Adding back activated T cells to purified infected B cells efficiently suppressed KSHV production, primarily due to CD4(+) T cells. This suppressive activity required T cell activation and direct cell-cell contact, but not prior exposure to KSHV antigen. Suppression was not MHC restricted and did not result in killing of the target cell. We therefore propose that oropharyngeal T cells activated by a variety of stimuli can recognize ligands on infected target B cells, leading to signaling events that prevent spontaneous lytic activation and promote latent infection in this compartment.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology, UCSF, San Francisco, California 94143, USA.
authors.forename: Jinjong
authors.initials: J
authors.lastname: Myoung
authors.forename: Don
authors.initials: D
authors.lastname: Ganem
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D015967:Gene Expression Regulation, Viral; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008280:Magnetics; D014066:Palatine Tonsil / Q000378:metabolism / Q000821:virology*; D015398:Signal Transduction; D017735:Virus Latency / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins