REGULATION OF HIGH MOBILITY GROUP PROTEINS BY KAPOSI’S SARCOMA ASSOCIATED HERPESVIRUS ENCODED LANA

Kaposi’s sarcoma associated herpesvirus (KSHV, HHV-8) is the etiological agent of Kaposi’s sarcoma (KS), and is tightly associated with primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). KSHV is a member of the gamma-herpesvirus family and can establish life-long latent infection in human B lymphocytes and endothelial cells. The latency-associated nuclear antigen (LANA) is among the few KSHV encoded genes during latency. LANA is expressed in all forms of KSHV infected cells and promotes host-cell survival and viral genome maintenance. Previously, we have found an interaction between LANA and HMGB1, an important chromatin protein which play roles in transcription regulation, DNA repair, and acts as a cytokine mediator of Inflammation. Here we show that in KSHV-infected cells, selected high mobility group (HMG) proteins are re-localized into distinct foci within the nucleus. Co-localization studies revealed that these HMG proteins are co-localized with LANA on the viral episomal genomes. As a transcription factor, HMGB1 interacts with the heterochromatin related histone 1, and regulates its interaction with the chromatin. We hypothesized that LANA interaction can modulate the interaction of HMGB1 with its partners, such as histone 1. Our data suggest that LANA regulates the interaction between HMGB1, histone 1 and chromatin. These findings suggest that LANA can disrupt the proper localization and function of HMGB1.