The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype.

RV1狂犬病病毒谱系成员KSHV和猕猴RFHVMn的潜伏期相关核抗原（LANA）与包含两分的富含KR的基序和富含RG的域的复杂核定位信号（NLS）的保存密切相关，后者的相互作用明显用进口蛋白α和ß1分别通过经典途径和非经典途径进行核进口。RV1 LANA在潜伏感染细胞的细胞核中表达，它们抑制复制并建立主要的RV1潜伏期。在这里，我们显示猕猴RRV和MneRV2来自更远相关的RV2谱系的LANA同源物，缺少富含KR的NLS，而是具有较大的富含RG的NLS，具有多个RG二肽和保守的RGG图案。RG-NLS与importinβ1独特地相互作用，后者介导RV2 LANA在核仁中的核输入和积累。