FIG. 2.

EBV infects B lymphocytes and induces and maintains their proliferation while expressing only a small subset of viral genes. One of these, LMP-1, is essential for driving their proliferation. It is expressed at widely different levels in individual cells within clonal populations of infected cells. These levels of expression are controlled by LMP-1's regulation of the UPR and autophagy. LMP-1 activates PERK, which phosphorylates eIF2α. This phosphorylation promotes expression of ATF4, which increases transcription of LMP-1's promoter. LMP-1's induction of the UPR leads to IRE-1's splicing of XBP-1, which is required for the secretion of the immunoglobulins observed in EBV-infected B cells. High levels of LMP-1 lead to the inhibition of general protein synthesis associated with the UPR and to the final stages of autophagy. This latter response fosters degradation of the high levels of LMP-1, lowering these levels to reset the cell's physiology such that LMP-1 can again drive proliferation and increase its own expression.