Viral and host factors drive a type 1 Epstein-Barr virus spontaneous lytic phenotype.
Viral and host factors drive a type 1 Epstein-Barr virus spontaneous lytic phenotype.
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EB病毒（EBV）是一种与癌症和自身免疫性疾病相关的γ-疱疹病毒，感染全球大多数成年人。在初始感染后，EBV通常在宿主中保持潜伏状态，具有最小的病毒基因表达。然而，这种原型潜伏病毒状态的畸变导致裂解性复制增加，可引起致癌因子的上调，促进EBV相关疾病。例如，鼻咽癌和移植后淋巴组织增生性疾病与EBV裂解性复制有很强的相关性。另一种与EBV相关的疾病，地方性伯基特淋巴瘤（BL），是一种生长极快的癌症，主要见于撒哈拉以南非洲疟疾流行地区的儿童。几乎所有地方性BL肿瘤都感染EBV，并且该疾病的标志是由于免疫球蛋白/Myc易位导致的致癌c-Myc表达水平高。在这项研究中，我们描述了自发溶解表型的EB病毒株从肯尼亚BL患者肿瘤。我们特别关注一种新的1型自发裂解型EBV毒株，并描述了可能导致这种表型的病毒和宿主因素。我们发现，感染自发裂解菌株的细胞具有较低的c-Myc蛋白稳定性，并表达高水平的浆细胞标志物SLAMF 7。此外，自发裂解菌株具有改变的潜伏状态，这似乎进一步促进其裂解表型。从地方性BL肿瘤中分离出自发裂解的EBV株提供了更多的证据，表明EBV可能不会在EBV相关疾病患者中保持原型潜伏状态，并提出了混杂裂解活性可能有助于这些疾病形成的可能性。EB病毒（EBV）感染了全球95%以上的成年人。鉴于其与各种癌症和自身免疫性疾病的联系，重要的是要了解EBV感染可能导致这些疾病的机制。在这项研究中，我们描述了一个不寻常的自发裂解表型在肯尼亚地方性伯基特淋巴瘤患者分离的EB病毒株。由于EBV的裂解性复制与各种疾病的发病机制有关，这些数据可以阐明参与这一过程的病毒和宿主因素。
Epstein–Barr virus (EBV) is a cancer and autoimmune disease-associated gamma-herpesvirus that infects the majority of adults worldwide. After initial infection, EBV generally maintains a latent state in the host with minimal viral gene expression. However, aberrations in this prototypical latent viral state leading to increased lytic replication can cause upregulation of oncogenic factors, promoting EBV-associated diseases. For example, nasopharyngeal carcinoma and post-transplant lymphoproliferative disease have strong associations with EBV lytic replication. Another EBV-associated disease, endemic Burkitt lymphoma (BL), is an extremely fast-growing cancer found primarily in children in malaria-endemic regions of Sub-Saharan Africa. Nearly all endemic BL tumors are infected with EBV and the hallmark of the disease is high levels of oncogenic c-Myc expression due to an immunoglobulin/Myc translocation. In this study, we describe spontaneous lytic phenotypes in EBV strains isolated from Kenyan BL patient tumors. We specifically focus on a novel Type 1 spontaneously lytic EBV strain and describe viral and host factors that could contribute to this phenotype. We found that cells infected with spontaneous lytic strains have lower c-Myc protein stability and express high levels of the plasma cell marker SLAMF7. Additionally, spontaneous lytic strains have altered latency states, which appear to further promote their lytic phenotypes. The isolation of spontaneously lytic EBV strains from endemic BL tumors provides more evidence that EBV may not maintain a prototypically latent state in patients with EBV-associated diseases and raises the possibility that promiscuous lytic activity may contribute to the formation of these diseases. Epstein–Barr virus (EBV) infects over 95% of adults worldwide. Given its connection to various cancers and autoimmune disorders, it is important to understand the mechanisms by which infection with EBV can lead to these diseases. In this study, we describe an unusual spontaneous lytic phenotype in EBV strains isolated from Kenyan endemic Burkitt lymphoma patients. Because lytic replication of EBV has been linked to the pathogenesis of various diseases, these data could illuminate viral and host factors involved in this process.
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影响因子：
6.7
作者：
Bristol JA;Djavadian R;Albright ER;Coleman CB;Ohashi M;Hayes M;Romero-Masters JC;Barlow EA;Farrell PJ;Rochford R;Kalejta RF;Johannsen EC;Kenney SC
通讯作者：
Kenney SC
DOI：
10.1093/bioinformatics/btp347
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Assefa S;Keane TM;Otto TD;Newbold C;Berriman M
通讯作者：
Berriman M
DOI：
10.1158/1541-7786.mcr-16-0305
发表时间：
2017-05
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kaymaz Y;Oduor CI;Yu H;Otieno JA;Ong'echa JM;Moormann AM;Bailey JA
通讯作者：
Bailey JA
影响因子：
82.9
作者：
Kelly, G;Bell, A;Rickinson, A
通讯作者：
Rickinson, A
影响因子：
5.4
作者：
Homa, Nicholas J.;Salinas, Raul;Luftig, Micah A.
通讯作者：
Luftig, Micah A.