Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL, 32610, USA.
Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL, 32610, USA; UF Genetics Institute, Gainesville, FL, 32610, USA; UF Health Cancer Center, Gainesville, FL, 32610, USA.
Virology. 2019 Oct;536:27-31. doi: 10.1016/j.virol.2019.07.028. Epub 2019 Jul 31.
The biology of primary lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection is still not well understood, which is largely attributed to the lack of cell lines permissive to robust lytic KSHV infection in vitro. Our study demonstrates that primary human dermal lymphatic microvascular endothelial cells (HDLMEC) support lytic KSHV replication following de novo infection, resulting in robust KSHV production, indicating that HDLMECs are suitable for studying the regulation of primary lytic KSHV infection. Importantly, by utilizing lytically infected HDLMECs, we show for the first time that the KSHV latent genes LANA and viral cyclin are required for lytic replication during de novo lytic infection, a function of these latent genes that has not yet been recognized. Since Kaposi's sarcoma is considered to be originated from infected lymphatic endothelial cells, HDLMECs represent a valuable in vitro cell culture model for investigating lytic KSHV infection, which has been understudied in KSHV pathogenesis.
原发性溶瘤性卡波西肉瘤相关疱疹病毒（KSHV）感染的生物学特性仍未得到很好的理解，这主要归因于缺乏允许体外有效溶瘤性 KSHV 感染的细胞系。我们的研究表明，原发性人真皮淋巴微脉管内皮细胞（HDLMEC）在初次感染后支持溶瘤性 KSHV 复制，导致大量 KSHV 的产生，表明 HDLMEC 适合用于研究原发性溶瘤性 KSHV 感染的调控。重要的是，通过利用溶瘤性感染的 HDLMEC，我们首次表明，在初次溶瘤性感染过程中，KSHV 的潜伏基因 LANA 和病毒细胞周期蛋白对于溶瘤复制是必需的，这是这些潜伏基因尚未被认识到的功能。由于卡波西肉瘤被认为起源于受感染的淋巴内皮细胞，因此 HDLMEC 代表了一种有价值的体外细胞培养模型，可用于研究 KSHV 发病机制中研究甚少的溶瘤性 KSHV 感染。
