Latent Kaposi’s Sarcoma-Associated Herpesvirus Infection of Monocytes Downregulates Expression of Adaptive Immune Response

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection is associated with the development of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. We report the establishment of a monocytic cell line latently infected with KSHV (KSHV-THP-1). We profiled viral and cytokine gene expression in the KSHV-THP-1 cells compared to that in unin-fected THP-1 cells and found that several genes involved in the host immune response were downregulated during latent infec-tion, including genes for CD80, CD86, and the cytokines tumor necrosis factor alpha (TNF-) and interleukin-1 (IL-1). Thus, KSHV minimizes its immunological signature by suppressing key immune response factors, enabling persistent infection and evasion from host detection. Kaposi’s sarcoma-associated herpesvirus (KSHV), also knownas human herpesvirus 8 (HHV8), is a member of the gamma-herpesvirus subfamily. KSHV is the etiological agent of Kaposi’s sarcoma (KS) (8), primary effusion lymphoma (PEL), and multi-centric variant of Castleman’s disease (MCD) (1, 8, 36). KS is a highly inflammatory and angiogenic vascular tumor defined by characteristic spindle cells, which are believed to originate from endothelial cells. PEL and MCD are both B cell lymphoprolifera-tive diseases