A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells.
A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells.
复制标题
作者：
致癌性γ疱疹病毒，包括人EB病毒（EBV）、人卡波西肉瘤相关疱疹病毒（KSHV）和鼠γ疱疹病毒68（MHV 68、γ HV 68、MuHV-4），与许多恶性肿瘤相关，包括B细胞淋巴瘤和鼻咽癌。这些病毒采用多种分子策略来定殖宿主，包括非编码RNA（ncRNA）的表达。作为第一个被鉴定的病毒ncRNA，EBV编码的RNA 1和2（分别为EBER 1和EBER 2）已经被广泛研究了几十年;然而，它们的特异性体内功能在很大程度上仍然未知。在这里的工作中，我们在体内互补系统中使用嵌合MHV 68病毒来测试EBV EBER 2是否有助于感染的急性和/或慢性阶段。来源于EBV株B 95 -8的EBER 2的表达导致体内潜伏感染的B细胞的显著扩增，这伴随着病毒感染的浆细胞的减少。EBV毒株通常携带EBER 2的两种变体之一，其主要区别在于最初在EBV毒株M81中鉴定的5-核苷酸核心多态性。引人注目的是，定义该核心多态性的5个核苷酸的突变导致受感染的B细胞扩增的丧失并恢复浆细胞感染。这项工作揭示了EBER 2的B 95 -8变体促进了体内潜伏感染的B细胞库的扩增，并且可能部分地通过抑制终末分化来实现。这些发现为病毒ncRNA促进体内定植的机制提供了新的见解，并进一步提供了与γ疱疹病毒操纵B细胞分化相关的固有致瘤风险的进一步证据。
The oncogenic gammaherpesviruses, including human Epstein-Barr virus (EBV), human Kaposi’s sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4), are associated with numerous malignancies, including B cell lymphomas and nasopharyngeal carcinoma. These viruses employ numerous molecular strategies to colonize the host, including the expression of noncoding RNAs (ncRNAs). As the first viral ncRNAs identified, EBV-encoded RNA 1 and 2 (EBER1 and EBER2, respectively) have been investigated extensively for decades; however, their specific in vivo functions remain largely unknown. In work here, we used chimeric MHV68 viruses in an in vivo complementation system to test whether EBV EBER2 contributes to acute and/or chronic phases of infection. Expression of EBER2 derived from EBV strain B95-8 resulted in a significant expansion of latently infected B cells in vivo, which was accompanied by a decrease in virus-infected plasma cells. EBV strains typically carry one of two variants of EBER2, which differ primarily by a 5-nucleotide core polymorphism identified initially in the EBV strain M81. Strikingly, mutation of the 5 nucleotides that define this core polymorphism resulted in the loss of the infected B cell expansion and restored plasma cell infection. This work reveals that the B95-8 variant of EBER2 promotes the expansion of the latently infected B cell pool in vivo and may do so in part through inhibition of terminal differentiation. These findings provide new insight into mechanisms by which viral ncRNAs promote in vivo colonization and further and provide further evidence of the inherent tumorigenic risks associated with gammaherpesvirus manipulation of B cell differentiation.
登录
查看更多内容
影响因子：
6.7
作者：
Liang X;Collins CM;Mendel JB;Iwakoshi NN;Speck SH
通讯作者：
Speck SH
影响因子：
5.4
作者：
Adler, H;Messerle, M;Koszinowski, UH
通讯作者：
Koszinowski, UH
影响因子：
5.4
作者：
ARRAND, JR;RYMO, L
通讯作者：
RYMO, L
影响因子：
15.3
作者：
Flaño, E;Kim, IJ;Blackman, MA
通讯作者：
Blackman, MA
影响因子：
5.4
作者：
Gong, Danyang;Dai, Xinghong;Sun, Ren
通讯作者：
Sun, Ren