Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.
Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.
复制标题
DOI：
10.14670/hh-30.559
复制
发表时间：
2015-05
影响因子：
2
通讯作者：
Samaniego F
中科院分区：
文献类型：
--
作者：
Berkova Z;Wang S;Sehgal L;Patel KP;Prakash O;Samaniego F
越来越多的证据支持人类疱疹病毒8，卡波西肉瘤相关疱疹病毒（KSHV），参与原发性渗出性淋巴瘤，多中心Castleman病和卡波西肉瘤的病理，但KSHV的确切机制的致癌过程的贡献仍然难以捉摸。我们研究了转基因小鼠表达的ORF K1的KSHV，其在KSHV基因组中的位置对应于其他疱疹病毒的已知淋巴增生基因。K1蛋白以前被证明含有组成型活性ITAM结构域，参与Akt和促生存信号的激活，并通过干扰FasL的结合来抑制Fas介导的凋亡。所有这些都表明K1在KSHV相关癌症的发病机制中可能发挥作用。K1转基因小鼠（80-90%）在8月龄和10月龄时出现淋巴样增生和脾肿大，25%确诊为淋巴瘤，50%在18月龄时出现腹部和/或肝脏肿瘤。组织学检查显示脾脏结构丧失和细胞结构增加。淋巴结显示结构破坏，滤泡消失和其他病理变化，包括血管滤泡淋巴样增生体征。其中一个肝脏有血管肉瘤的迹象。总之，我们的组织学结果显示K1转基因小鼠的病理变化类似于淋巴瘤，Castleman病和血管肉瘤，表明K1可能有助于KSHV相关癌症的发展。
Growing evidence supports the involvement of human herpervirus 8, Kaposi’s sarcoma associated herpesvirus (KSHV), in the pathology of primary effusion lymphoma, multicentric Castleman’s disease, and Kaposi’s sarcoma, but the exact mechanism of KSHV contribution to the oncogenic process remains elusive. We studied transgenic mice expressing the ORF K1 of KSHV, whose position in the KSHV genome corresponds to known lymphoproliferative genes of other herpesviruses. K1 protein was previously shown to contain a constitutively active ITAM domain, involved in activation of Akt and pro-survival signaling, and to inhibit Fas-mediated apoptosis by interfering with binding of FasL. All this pointed to a possible role of K1 in the pathogenesis of KSHV-associated cancers. K1 transgenic mice (80–90%) developed lymphoid hyperplasia and splenomegaly at 8 and 10 months of age, 25% had confirmed diagnosis of lymphoma, and 50% developed abdominal and/or hepatic tumors by 18 months of age. Histological examination showed loss of splenic architecture and increased cellularity. Lymph nodes showed disrupted architecture with effaced follicles and other pathological changes, including signs of angiofollicular lymphoid hyperplasia. One of the livers showed signs of angiosarcoma. In summary, our histology results revealed pathological changes in K1 transgenic mice similar to lymphoma, Castleman’s disease, and angiosarcoma, suggesting that K1 may contribute to the development of KSHV-associated cancers.