Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Med Virol. 2024 Aug;96(8):e29869. doi: 10.1002/jmv.29869.
Epstein-Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV-encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22-like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1-containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.
EB 病毒（EBV）是一种非常成功的病原体，感染了约 95%的成年人，与多种癌症和自身免疫性疾病有关。潜伏感染细胞中最丰富的病毒因子不是蛋白质，而是一种称为 EBV 编码的 RNA1（EBER1）的非编码 RNA。尽管 EBER1 含量非常丰富，并且在四十多年前就被发现，但它的功能仍然难以捉摸。EBER1 与核糖体蛋白 L22 相互作用，而 L22 通常会抑制其同源物 L22 样 1（L22L1）的表达。在这里，我们表明当 L22 结合 EBER1 时，它不能抑制 L22L1，导致 L22L1 被表达并整合到核糖体中。我们进一步表明，含有 L22L1 的核糖体优先翻译参与氧化磷酸化途径的 mRNA。此外，在 EBV 感染静止 B 细胞时，上调 L22L1 对于生长转化和永生化是不可或缺的。总之，我们的结果表明，EBER1 的功能是在翻译水平上调节宿主基因表达，从而避免了调节宿主基因转录的需要。
