Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman disease. The tegument is a structure that is unique to herpesviruses that includes host and viral proteins, including the viral ORF42 and ORF55 proteins. Alphaherpesvirus tegument proteins have been well studied, but much is unknown regarding KSHV. Here, we report an interaction between the ORF42 and ORF55 proteins. ORF55 interacted with and recruited ORF42 from the nucleus to the cytoplasm. When ORF42 and ORF55 were expressed simultaneously in cultured cells, the expression level of these two viral proteins was higher than when either was expressed independently. ORF55, but not ORF42, was polyubiquitinated, suggesting that an unidentified regulatory mechanism may be present. A recombinant virus with an ectopic stop codon in ORF42 exhibited normal replication of genomic DNA, but fewer virus particles were released with the recombinant than with the wild-type virus. A unique R136Q mutation in ORF42, which is found in a KSHV strain that is prevalent on Miyako Island, Okinawa Prefecture, Japan, further increased the expression of ORF42 and ORF55 when these proteins were expressed simultaneously. However, the ORF42 R136Q mutation did not affect the localization pattern of ORF42 itself or of ORF55. In addition, experiments with a recombinant virus possessing the ORF42 R136Q mutation showed lower levels of production of the mutant virus than of the wild-type virus, despite similar levels of genome replication. We suggest that the R136Q mutation in ORF42 plays an important role in ORF55 protein expression and virus production.

卡波西肉瘤相关疱疹病毒 (KSHV) 引起卡波西肉瘤、原发性渗出性淋巴瘤和多中心卡斯尔曼病。被膜是疱疹病毒特有的结构，包括宿主和病毒蛋白，包括病毒 ORF42 和 ORF55 蛋白。阿尔法疱疹病毒外皮蛋白已得到充分研究，但关于 KSHV 的了解还很多。在这里，我们报告了 ORF42 和 ORF55 蛋白之间的相互作用。 ORF55 与 ORF42 相互作用并将 ORF42 从细胞核募集到细胞质。当ORF42和ORF55在培养细胞中同时表达时，这两种病毒蛋白的表达水平比单独表达时更高。 ORF55（而非 ORF42）被多泛素化，表明可能存在未知的调控机制。 ORF42 中具有异位终止密码子的重组病毒表现出基因组 DNA 的正常复制，但与野生型病毒相比，重组病毒释放的病毒颗粒较少。在日本冲绳县宫古岛流行的 KSHV 毒株中发现了 ORF42 中独特的 R136Q 突变，当 ORF42 和 ORF55 同时表达时，这两种蛋白的表达进一步增加。然而，ORF42 R136Q突变并不影响ORF42本身或ORF55的定位模式。此外，使用具有 ORF42 R136Q 突变的重组病毒进行的实验表明，尽管基因组复制水平相似，但突变病毒的产量水平低于野生型病毒。我们认为 ORF42 中的 R136Q 突变在 ORF55 蛋白表达和病毒产生中发挥重要作用。