Epstein-Barr virus LF2 protein regulates viral replication by altering Rta subcellular localization.

Journal of Virology
Andreas M F HeilmannEric Johannsen

Abstract

The switch from Epstein-Barr virus (EBV) latent infection to lytic replication is governed by two viral transactivators, Zta and Rta. We previously reported that the EBV protein LF2 binds Rta, inhibits Rta promoter activation, and blocks EBV replication in cells. In addition, LF2 induces SUMO2/3 modification of Rta. We now show that this modification occurs at four lysines within the Rta activation domain (426, 446, 517, and 530) and that sumoylation of Rta is not essential for its repression. Coexpression studies demonstrated that Rta is sequestered to the extranuclear cytoskeleton in the presence of LF2. We mapped the LF2 binding site to Rta amino acids (aa) 476 to 519 and showed that LF2 binding is critical for Rta relocalization and repression. The core of this binding site, Rta aa 500 to 526, confers LF2-mediated relocalization and repression onto the artificial transcription factor GAL4-VP16. Mutational analysis of LF2 provided further evidence that Rta redistribution is essential for repression. Rta localization changes during replication of the LF2-positive P3HR1 genome, but not during replication of the LF2-negative B95-8 genome. BLRF2 protein expression was decreased and delayed in P3HR1 cells compared with B95-8 cell...Continue Reading

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Citations

Mar 2, 2012·Journal of Virology·Andreas M F HeilmannEric Johannsen
Jan 18, 2013·PloS One·Ya-Chun Yang, Li-Kwan Chang
Mar 19, 2013·The Journal of Biological Chemistry·Ya-Chun YangLi-Kwan Chang
Aug 25, 2015·The Journal of General Virology·Chen-Chia HungShih-Tung Liu
Feb 14, 2014·Journal of Virology·Tawin IemprideeJanet E Mertz
Apr 23, 2015·The Journal of General Virology·Ya-Chun YangLi-Kwan Chang
Jul 10, 2020·Journal of Virology·Richard J KrausJanet E Mertz
Jan 21, 2017·Frontiers in Microbiology·Hsiang-Hung HuangLi-Kwan Chang
Jan 6, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna E CoghillDenise L Doolan
Mar 5, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Lusheng SongCharles S Rabkin

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