Persistent intranuclear infection is an uncommon infection strategy among RNA viruses. However, Borna disease virus 1 (BoDV-1), a nonsegmented, negative-strand RNA virus, maintains viral infection in the cell nucleus by forming structured aggregates of viral ribonucleoproteins (vRNPs), and by tethering these vRNPs onto the host chromosomes. To better understand the nuclear infection strategy of BoDV-1, we determined the host protein interactors of the BoDV-1 large (L) protein. By proximity-dependent biotinylation, we identified several nuclear host proteins interacting with BoDV-1 L, one of which is TRMT112, a partner of several methyltransferases (MTases). TRMT112 binds with BoDV-1 L at the RNA-dependent RNA polymerase domain, together with BUD23, an 18S ribosomal RNA MTase and 40S ribosomal maturation factor. We then discovered that BUD23–TRMT112 mediates the chromosomal tethering of BoDV-1 vRNPs, and that the MTase activity is necessary in the tethering process. These findings provide us a better understanding on how nuclear host proteins assist the chromosomal tethering of BoDV-1, as well as new prospects of host–viral interactions for intranuclear infection strategy of orthobornaviruses.

中文翻译：

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BUD23–TRMT112 与博尔纳病病毒的 L 蛋白相互作用并介导病毒核糖核蛋白的染色体束缚

持续性核内感染是 RNA 病毒中不常见的感染策略。然而，博尔纳病病毒 1 (BoDV-1) 是一种非分段的负链 RNA 病毒，通过形成病毒核糖核蛋白 (vRNP) 的结构化聚集体并将这些 vRNP 束缚在宿主染色体上来维持细胞核中的病毒感染。为了更好地了解 BoDV-1 的核感染策略，我们确定了 BoDV-1 大 (L) 蛋白的宿主蛋白相互作用物。通过邻近依赖性生物素化，我们鉴定了几种与 BoDV-1 L 相互作用的核宿主蛋白，其中一种是 TRMT112，它是几种甲基转移酶 (MTases) 的伙伴。TRMT112 在 RNA 依赖的 RNA 聚合酶结构域与 BoDV-1 L 结合，以及 BUD23、18S 核糖体 RNA MTase 和 40S 核糖体成熟因子。然后我们发现 BUD23–TRMT112 介导 BoDV-1 vRNP 的染色体束缚，并且 MTase 活性在束缚过程中是必需的。这些发现使我们更好地了解核宿主蛋白如何协助 BoDV-1 的染色体束缚，以及宿主-病毒相互作用对原发性病毒核内感染策略的新前景。