Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO 80045, USA.
Cell Rep. 2023 Jul 25;42(7):112767. doi: 10.1016/j.celrep.2023.112767. Epub 2023 Jul 12.
Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous. Elevated circulating monocytes are common in these parasitic infections. Here, we show that KSHV infection of monocytes or M-CSF-differentiated (M2) macrophages is highly efficient. Proteomic analyses demonstrate that infection induces macrophage production of B cell chemoattractants and activating factor. We find that KSHV acts with monocytes or M2 macrophages to stimulate B cell survival, proliferation, and plasmablast differentiation. Further, macrophages drive infected plasma cell differentiation and long-term viral latency. In Kenya, where KSHV is endemic, we find elevated monocyte levels in children with malaria. These findings demonstrate a role for mononuclear phagocytes in KSHV B cell latency and suggest that mononuclear phagocyte abundance may underlie KSHV's geographic disparity.
卡波西肉瘤疱疹病毒（KSHV）建立终身感染并潜伏在受感染的 B 细胞中。矛盾的是，体外 B 细胞感染效率低下，细胞迅速死亡，表明缺乏必要的因素。KSHV 的流行病学与疟疾和某些寄生虫感染非常相似，而其他疱疹病毒则无处不在。在这些寄生虫感染中，循环单核细胞升高很常见。在这里，我们表明 KSHV 对单核细胞或 M-CSF 分化（M2）巨噬细胞的感染非常有效。蛋白质组学分析表明，感染诱导巨噬细胞产生 B 细胞趋化因子和激活因子。我们发现 KSHV 与单核细胞或 M2 巨噬细胞一起作用，刺激 B 细胞的存活、增殖和浆母细胞分化。此外，巨噬细胞驱动受感染的浆细胞分化和长期病毒潜伏。在 KSHV 流行的肯尼亚，我们发现患有疟疾的儿童单核细胞水平升高。这些发现表明单核吞噬细胞在 KSHV B 细胞潜伏中起作用，并表明单核吞噬细胞的丰度可能是 KSHV 地理差异的基础。
