Final Envelopement of Epstein-Barr Virion

Epstein-Barr virus (EBV) infects B lymphocyte and epithelial cells. The infections are commonly persistent and latent. However, the virus must go through a lytic stage to produce progenies to establish new infection. During the lytic cycle, viral DNA and proteins are produced, then DNA is packaged into capsid in the nucleus. Viral glycoprotein-embedded envelope then adds onto the nucleocapsid during maturation, including processes of primary envelopment, de-envelopment and final envelopment. Our earlier study showed that BBLF1 is involved in final envelopment. My recent study identifies that BGLF2, which is a tegument protein associated with capsids, interacts with BBLF1. The interaction promotes translocation of cytosolic BGLF2 to the TGN membrane, where BBLF1 and viral glycoproteins are present. Therefore, this study posits that BBLF1 acts as bridge by interacting with BGLF2 and glycoproteins, thus recruiting BGLF2-coated capsids to glycoprotein-embedded TGN membrane. Ultimately, the interactions among BBLF1, BGLF2, and glycoproteins on TGN membrane promote the budding of capsids into the lumen. The interaction between BBLF1 and BGLF2 is an important event occurring during final envelopment, this study will establish a sensor based on this interaction that allow us to monitor the dynamic events of final envelopment in vivo. A recent study showed that BGLF2 may interact with several viral lytic proteins, including capsid protein, BKRF4, BTRF1 and glycoproteins, suggesting BGLF2 serves as an interaction hub that is involved in final envelopment. The cells expressed BGLF2 shRNA will be established and studies regarding to the interactions and regulatory mechanisms between BGLF2, capsids, teguments and host factors will be conducted. An earlier study showed that at least 11 glycoproteins are incorporated into the virion. This study will investigate how these glycoproteins are transported to the site, the TGN/endosome derived membrane, for final envelopment. In addition, BBLF1 is a dual-acylated modified protein and is located at the TGN and the lipid rafts, suggesting that lipid rafts serves as a platform during final envelopment. The relationship between lipid rafts and final envelopment and the mechanism of glycoprotein targeting to TGN or lipid raft will be investigated by this study. The results from these studies will provide a better understanding in final envelopment during EBV lytic cycle.

Project ID:PC10601-0874
External Project ID:MOST105-2320-B182-014-MY2