Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599.
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11379-E11387. doi: 10.1073/pnas.1810128115. Epub 2018 Nov 14.
Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV/EBV PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein-Barr nuclear antigen 1 (EBNA-1) , even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression.
原发性渗出性淋巴瘤（PEL）是一种 B 细胞淋巴瘤，它总是与卡波西肉瘤相关疱疹病毒（KSHV）有关，在许多情况下也与 EBV 有关；然而，对于 EBV 合并感染的要求尚不清楚。在这里，我们证明了向 KSHV 单阳性 PEL 添加外源性 EBV 会导致 KSHV 基因组维持和 KSHV 潜伏相关核抗原（LANA）表达增加。为了表明 EBV 对于自然合并感染的 PEL 是必需的，我们用 EBV 特异性 CRISPR/Cas9 质粒核转染 KSHV/EBV PEL 细胞系以删除 EBV，并观察到细胞活力、KSHV 基因组拷贝数和 LANA 表达的显著下降。即使 EBNA-1 和 LANA 不在感染细胞中共定位，表达 Epstein-Barr 核抗原 1（EBNA-1）也可以逆转这种表型。这项工作揭示了 EBV EBNA-1 通过增加 KSHV 病毒载量和 LANA 表达在 PEL 的发病机制中起着至关重要的作用。
