Kaposi’s Sarcoma-associated Herpesvirus Selectively Infects a Subset of

• KSHV infects tonsillar B cells ex vivo. KSHV genomic DNA remains associated with tonsillar B cells up to 1 week following exposure. Furthermore, KSHV prelatent transcripts are detectable in these cells, with levels peaking at 24hpi. Finally, the latency associated nuclear antigen, LANA, is expressed with characteristic punctate nuclear morphology at least one week following exposure to KSHV. • KSHV selectively infects λ tonsillar B cells ex vivo. Not only were tonsillar B cells preferentially susceptible to KSHV latent infection over the non-B cell subsets in the tonsil (primarily T cells, monocytes and dendritic cells), but specifically, the λ subset of tonsillar B cells, and not the κ subset, contained nearly all of the latent infection. This is not only the first report of viral tropism based on differential allelic expression, but also one of the first suggestions that λ and κ B cells may differ phonotypically. • Ex vivo KSHV-infected B cells are IgM+ and 38 % express CD27. These cells resemble, and thus may be the precursors to, Multicentric Castleman’s disease B cells. • B cells proliferate following infection with the KSHV. Latently infected cells are larger, contain more DNA and preferentially express the proliferation antigen, Ki67 as compared to the non-infected cells in the same culture, as well as cells that were not exposed to KSHV. • KSHV-infected B cells express high levels of IL-6R. Nearly all infected B cells expressed IL-6R and expression was proportional to the number of viral genomes present in individual cells. IL-6, both human and viral, have been implicated in the pathogenesis of Multicentric Castleman’s diseae and ex vivo infected B cells similarly appear able to respond to this cytokine