Cell dynamics and immune response to BLV infection: a unifying model
Cell dynamics and immune response to BLV infection: a unifying model
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DOI：
10.2741/2165
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Willems, Luc
中科院分区：
文献类型：
--
作者：
Florins, Arnaud;Gillet, Nicolas;Willems, Luc
牛白血病病毒（BLV）是引起牛淋巴组织增生性疾病的天然病原体。BLV也可以通过实验传播到相关的反刍动物物种，绵羊，其中发病机制更为急性。尽管这两种易感物种都产生了强烈的抗病毒免疫应答，但病毒在整个生命过程中无限期地持续存在，显然处于转录沉默阶段，至少在一部分感染细胞中是如此。感染后不久，这些体液和细胞毒性活性非常有效地消除了病毒复制周期，只允许携带前病毒的细胞进行有丝分裂扩增。这些感染细胞的短期培养最初表明，病毒表达可防止自发性细胞凋亡，表明白血病是一个长寿命细胞积累的过程。这一结论最近被重新考虑后，在体内动态研究的基础上灌注核苷（溴脱氧尿苷）或荧光蛋白标记物（CFSE）。在绵羊中，受感染细胞的周转率增加，表明免疫系统发挥了永久清除过程。淋巴细胞往返于次级淋巴器官是维持细胞稳态的关键组成部分。免疫选择压力的最终结果是，只有病毒在转录上沉默的细胞才能存活和积累，最终导致淋巴细胞增多。用脱乙酰酶抑制剂激活该沉默储库中的病毒和/或细胞表达导致前病毒负载的崩溃。换句话说，病毒表达的调节似乎在淋巴细胞绵羊中是治愈性的，这是一种在感染相关的人类嗜T淋巴细胞病毒1型的患者中也可能有效的方法。总之，BLV和宿主免疫应答之间的动态相互作用调节（i）驱动（或）有利于增殖的病毒表达和（ii）防止细胞凋亡的病毒沉默之间的复杂平衡。作为结论，我们提出了一个假设的模型统一所有这些机制。
Bovine Leukemia virus ( BLV) is the natural etiological agent of a lymphoproliferative disease in cattle. BLV can also be transmitted experimentally to a related ruminant species, sheep, in which the pathogenesis is more acute. Although both susceptible species develop a strong anti- viral immune response, the virus persists indefinitely throughout life, apparently at a transcriptionally silent stage, at least in a proportion of infected cells. Soon after infection, these humoral and cytotoxic activities very efficiently abolish the viral replicative cycle, permitting only mitotic expansion of provirus- carrying cells. Short term cultures of these infected cells initially indicated that viral expression protects against spontaneous apoptosis, suggesting that leukemia is a process of accumulation of long- lived cells. This conclusion was recently reconsidered following in vivo dynamic studies based on perfusions of nucleoside ( bromodeoxyuridine) or fluorescent protein markers ( CFSE). In sheep, the turnover rate of infected cells is increased, suggesting that a permanent clearance process is exerted by the immune system. Lymphocyte trafficking from and to the secondary lymphoid organs is a key component in the maintenance of cell homeostasis. The net outcome of the immune selective pressure is that only cells in which the virus is transcriptionally silenced survive and accumulate, ultimately leading to lymphocytosis. Activation of viral and/ or cellular expression in this silent reservoir with deacetylase inhibitors causes the collapse of the proviral loads. In other words, modulation of viral expression appears to be curative in lymphocytic sheep, an approach that might also be efficient in patients infected with the related Human T- lymphotropic virus type 1. In summary, a dynamic interplay between BLV and the host immune response modulates a complex equilibrium between ( i) viral expression driving ( or) favoring proliferation and ( ii) viral silencing preventing apoptosis. As conclusion, we propose a hypothetical model unifying all these mechanisms.