The Epstein-Barr virus (EBV) protein EB2 is an mRNA export factor essential for virus production

The EBV early protein EB2 (aka Mta, SM and BMLF1) shares properties with mRNA export factors. It shuttles between the cytoplasm and the nucleus, and interacts with RNA both in vitro and in vivo but with no apparent sequence specificity. EB2 induces the cytoplasmic accumulation of mRNAs generated from intronless and intron-containing genes, likely through interactions with cellular export factors of the TAP/p15 pathway. Using a cell line carrying a viral genome with the EB2 gene deleted, it has been shown that EB2 is essential for the production of infectious virions by facilitating the nuclear export of a subset of early and late viral mRNAs, a function regulated by CK2 phosphorylation of EB2. There are docking sites for both CK2 subunits and for the heterotetrameric enzyme in the EB2 N- and C-terminal domains. Accordingly, EB2 and CK2 co-purify as a complex in which CK2 phosphorylates EB2. CK2 phosphorylation of EB2 at one of the Ser-55, Ser-56 and ser-57 is critical for its mRNA export function and as a consequence, for infectious virus production.