Host-Level Susceptibility and IRF1 Expression Influence the Ability of IFN-gamma to Inhibit KSHV Infection in B Lymphocytes

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi's sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-gamma has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naive B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-gamma in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-gamma-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection.