Fanxiu Zhu

My laboratory studies Kaposi's sarcoma–associated herpesvirus (KSHV), a human DNA tumor virus associated with several human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. We are interested in viral proteins that are localized in the tegument layer, a space between capsid and envelope in the viral particles. The tegument comprises at least a dozen proteins that are delivered into cells upon infection, so they have the opportunity to exert their functions at the very beginning in the infection process. The unique temporal and spatial expressions of tegument proteins put them in the forefront of coping with the host cellular environment. We found that KSHV ORF45, an abundant gammaherpesvirus-specific tegument protein, interacts with interferon regulatory factor 7 (IRF-7) and antagonizes the host innate antiviral responses. We also revealed that ORF45 interacts with p90 ribosomal S6 kinases (RSKs) and modulates the ERK/RSK MAPK signaling pathway, which plays critical roles in KSHV lytic replication. More recently, we discovered ORF52, another abundant gammaherpesvirus-specific tegument protein, as the first viral inhibitor of the host major cytosolic DNA sensor cGAS (cyclic GMP-AMP synthase). We therefore proposed to rename it KicGAS (KSHV inhibitor of cGAS). We are now exploring the mechanisms by which these KSHV tegument proteins evade the host innate antiviral responses and modulate the host intracellular kinase signaling pathways. We are also interested in the structural analysis of herpesvirus tegument by CryoEM. The structural organization and morphogenesis of herpesviral tegument are largely unknown. We use various approaches to investigate why and how viral proteins are selectively assembled into the tegument layer.