Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain.
Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain.
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DOI：
10.1128/mbio.02410-20
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发表时间：
2020-09-29
期刊：
影响因子：
6.4
通讯作者：
Kalejta RF
中科院分区：
文献类型：
--
作者：
Lyon SM;Yetming KD;Paulus C;Nevels M;Kalejta RF
人巨细胞病毒（HCMV）是导致出生缺陷的主要传染性原因，是免疫功能低下的HIV/AIDS和器官移植患者的严重并发症，并且有助于免疫衰老和心血管疾病。HCMV还涉及癌症如多形性胶质母细胞瘤（GBM），并感染离体培养的GBM肿瘤细胞。在分裂的肿瘤细胞中，DNA肿瘤病毒的基因组在有丝分裂期间核膜破裂后重新获得核定位。这种有丝分裂存活是由具有染色质束缚结构域（CTD）的病毒蛋白介导的。在这里，我们报告说，HCMV基因组保持在分裂成纤维细胞的CTD的病毒IE 19蛋白。在生产性感染期间发现病毒基因组维持因子可以帮助解释HCMV阳性肿瘤内以及潜伏期期间的病毒基因组动态。DNA肿瘤病毒的基因组在有丝分裂期间核膜破裂后通过具有染色质束缚结构域（CTD）的病毒蛋白的作用重新获得核定位。在这里，我们报告说，人巨细胞病毒（HCMV）基因组在有丝分裂过程中维持的CTD的病毒IE 19蛋白。IE 19 CTD的缺失或IE 19剪接受体位点的破坏减少了分裂成纤维细胞感染期间病毒基因组的维持和子代病毒体的形成，这两者都被IE 19异位表达所拯救。在生产性感染过程中发现病毒基因组维持因子，为研究与出生缺陷、器官移植失败和癌症有关的HCMV感染模式提供了新的见解。
Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, represents a serious complication for immunocompromised HIV/AIDS and organ transplant patients, and contributes to both immunosenescence and cardiovascular diseases. HCMV is also implicated in cancers such as glioblastoma multiforme (GBM) and infects ex vivo-cultured GBM tumor cells. In dividing tumor cells, the genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis. This mitotic survival is mediated by a viral protein with a chromatin-tethering domain (CTD). Here, we report that the HCMV genome is maintained in dividing fibroblasts by the CTD of the viral IE19 protein. The discovery of a viral genome maintenance factor during productive infection could help explain viral genome dynamics within HCMV-positive tumors as well as during latency. The genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of the viral IE19 protein. Deletion of the IE19 CTD or disruption of the IE19 splice acceptor site reduced viral genome maintenance and progeny virion formation during infection of dividing fibroblasts, both of which were rescued by IE19 ectopic expression. The discovery of a viral genome maintenance factor during productive infection provides new insight into the mode of HCMV infection implicated in birth defects, organ transplant failure, and cancer.