FIG 8.

Schematic model showing regulation of LANA expression through G-quadruplex formation and antigen presentation. LANA is required for maintaining the viral genome in latent cells, and its expression is modulated by the level of LANA in the cells. At lower levels of LANA, hnRNP A1 binds to the G-quadruplex region of LANA mRNA and exports it to the cytoplasm following destabilization of the G-quadruplex structures for translation. Once a sufficient or higher level of LANA is synthesized and translocated to the nucleus, it binds to the G-quadruplex region of the LANA mRNA and retains the G-quadruplex-forming mRNAs in the nucleus to control an excess synthesis of LANA protein. G-quadruplex-mediated control of LANA mRNA translation ensures optimal expression without overly producing mature or defective ribosomal proteins (DriPs), which are presented through MHC class I molecules to escape the host’s immune surveillance system.