Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia Health Systems, Charlottesville, Virginia, USA.
J Clin Invest. 2011 Feb;121(2):752-68. doi: 10.1172/JCI44185. Epub 2011 Jan 18.
Kaposi sarcoma-associated herpesvirus (KSHV; also known as HHV8) is the causative agent of two B cell tumors, multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). However, little is known about the nature of the specific B cell subtype(s) most susceptible to infection. Identifying these cells would provide direct insight into KSHV transmission and virus-induced transformation. To identify this subset and to determine whether infection alters its cellular phenotype, we exposed human tonsillar cells to KSHV and characterized infected cells using high-throughput multispectral imaging flow cytometry (MIFC). Stable expression of the virally encoded latency-associated nuclear antigen (LANA), a marker of latent KSHV infection, was observed predominantly in cells expressing the l light chain of the B cell receptor. These LANA+ B cells proliferated and exhibited similarities to the cells characteristic of MCD (IgMl-expressing plasmablasts), including blasting morphology with elevated expression of Ki67, variable expression of CD27, and high levels of IgM and IL-6 receptor. Furthermore, the proportion of infected cells showing a blasting phenotype increased upon addition of exogenous IL-6. Our data lead us to propose that oral transmission of KSHV involves the latent infection of a subset of tonsillar IgMl-expressing B cells, which then proliferate as they acquire the plasmablast phenotype characteristic of MCD.
卡波西肉瘤相关疱疹病毒（KSHV；也称为 HHV8）是两种 B 细胞肿瘤，多中心 Castleman 病（MCD）和原发性渗出性淋巴瘤（PEL）的病原体。然而，对于最易感染的特定 B 细胞亚群的性质知之甚少。鉴定这些细胞将为 KSHV 的传播和病毒诱导的转化提供直接的见解。为了鉴定该亚群并确定感染是否改变其细胞表型，我们使人类扁桃体细胞暴露于 KSHV 并使用高通量多光谱成像流式细胞术（MIFC）对感染的细胞进行了表征。病毒编码的潜伏相关核抗原（LANA）的稳定表达，这是潜伏 KSHV 感染的标志物，主要在表达 B 细胞受体的 l 轻链的细胞中观察到。这些 LANA+ B 细胞增殖，并表现出与 MCD 特有的细胞相似性（表达 IgMl 的浆母细胞），包括具有升高的 Ki67 表达的爆燃形态、CD27 表达的可变性以及高水平的 IgM 和 IL-6 受体。此外，在添加外源性 IL-6 后，表现出爆燃表型的感染细胞的比例增加。我们的数据表明，KSHV 的口腔传播涉及扁桃体 IgMl 表达 B 细胞的亚群的潜伏感染，然后在获得 MCD 特征性的浆母细胞表型时增殖。
