卡波西肉瘤相关疱疹病毒（KSHV）是一种致癌性疱疹病毒，与卡波西肉瘤的发展直接相关。 KSHV 在 B 细胞中建立潜伏感染，可以重新激活该细胞以启动裂解复制，产生感染性病毒颗粒。使用药理学和遗传沉默方法，我们发现 B 细胞中的电压门控 K 通道 Kv1.3 增强了 KSHV 裂解性复制。 KSHV 复制和转录激活剂 (RTA) 蛋白增加了 Kv1.3 的丰度，并导致 K 通道活性增强和 B 细胞膜超极化。增强的 Kv1.3 活性促进细胞内 Ca2+ 内流，导致 Ca2+ 驱动的 KSHV RTA 和活化 T 细胞核因子 (NFAT) 蛋白的核定位，随后增加 NFAT1 靶基因的表达。 Kv1.3 阻断剂或沉默可抑制 KSHV 裂解性复制和感染性病毒颗粒的产生。这些发现强调 Kv1.3 作为可药物宿主因子，是 KSHV 裂解复制成功完成的关键。

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi's sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K+ channel Kv1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of Kv1.3 and led to enhanced K+ channel activity and hyperpolarization of the B cell membrane. Enhanced Kv1.3 activity promoted intracellular Ca2+ influx, leading to the Ca2+-driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by Kv1.3 blockers or silencing. These findings highlight Kv1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication.