Modeling adenovirus latency in human lymphocyte cell lines.
Modeling adenovirus latency in human lymphocyte cell lines.
复制标题
模拟人淋巴细胞系中的腺病毒潜伏期。
DOI：
10.1128/jvi.00562-10
复制
发表时间：
2010
影响因子：
5.4
通讯作者：
Gooding,LindaR
中科院分区：
文献类型：
--
作者：
Zhang,Yange;Huang,Wen;Ornelles,DavidA;Gooding,LindaR
C 种腺病毒在扁桃体和腺样体的淋巴细胞中建立潜伏感染。为了了解这种裂解病毒如何在这些细胞中维持，我们检查了支持整个病毒生命周期的四种人类淋巴细胞系。 T 细胞系 Jurkat 在病毒感染后不久就停止增殖并死亡。 BJAB、Ramos（B 细胞）和 KE37（T 细胞）在复制病毒基因组的同时继续以接近正常的速度分裂。感染后 130 至 150 天，BJAB 细胞中的病毒基因组数量达到峰值，然后下降到每个细胞一个基因组以下。在相当一段时间内，Ramos 和 KE37 细胞将每个细胞的病毒基因组维持在 100 多个拷贝。 BJAB 细胞将病毒 DNA 维持为单体附加体。所有三种持续感染的细胞在感染后 24 小时内都失去了细胞表面柯萨奇和腺病毒受体 (CAR) 的表达，并且 CAR 表达在感染后至少 340 天内保持低水平。 CAR 损失通过两个阶段过程进行。首先，细胞表面染色的最初丧失需要病毒晚期基因表达和 CAR 结合纤维蛋白，即使 CAR 蛋白和 mRNA 水平仍然很高。其次，CAR mRNA 在感染后约 30 天消失，即使病毒 DNA 从细胞中丢失后仍保持较低水平。在感染后后期（第180天），即使通过逆转录病毒转导将CAR重新引入细胞，BJAB细胞也不能被腺病毒再次感染，这表明感染后这些细胞中多个基因的表达已稳定改变。
Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR-binding fiber protein even while CAR protein and mRNA levels remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection.