Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto Nacional de Tecnología Agropecuaria (INTA), Instituto de Virología. Nicolás Repetto y De los Reseros (s/n), Hurlingham (CP1686), Buenos Aires, Argentina.
BMC Vet Res. 2019 May 16;15(1):150. doi: 10.1186/s12917-019-1908-7.
The absence of virus expression during the chronic stage of bovine leukemia virus (BLV) infection and its reactivation upon ex vivo culture has become a long-lived Dogma. During the chronic stage of BLV infection the immune response limits viral replication and the mitotic division of latently infected cells, carrying BLV provirus, allows viral expansion and disease progression towards a lymphoproliferative disorder. Several stressor factors have been associated with animal production and handling. As natural mediator of stress, glucocorticoids are strong immunosuppressive agents; moreover, they can bind long-terminal repeat region of retroviruses and induce viral expression. In the present study, we present a case report describing the spontaneous reactivation of BLV infection in naturally infected cattle.
In order to investigate if virus reactivation occurred in vivo during the course of BLV infection, we followed up for 328 days one Holstein cow (> 3 years) chronically infected with BLV which presented high-proviral loads. This animal was neither lactating nor pregnant. Furthermore, we investigated if a stressor stimulus, in this case the administration of a synthetic glucocorticoid (dexamethasone), could impact the course of BLV infection in three additional cattle. For the first time, we observed a high level of BLV transcripts in a total of four cattle chronically infected with BLV. The detection of viral transcripts corresponding to pol gene strongly suggests virus reactivation in these animals. Interestingly, this simultaneous virus reactivation was unrelated to dexamethasone treatment.
We reported for the first time spontaneous and high level of BLV transcriptional activation in cattle chronically infected with BLV. Although virus reactivation was unrelated to dexamethasone treatment, other stressor stimuli might have influenced this outcome. Future studies will be necessary to understand these observations, since the spontaneous virus reactivation presented here might have implications on BLV pathogenesis and transmission.
牛白血病病毒 (BLV) 感染的慢性期缺乏病毒表达及其在体外培养时的重新激活已成为一个长期存在的定论。在 BLV 感染的慢性期,免疫反应限制了病毒的复制,潜伏感染细胞的有丝分裂分裂使 BLV 前病毒得以扩增,并导致疾病向淋巴增生性疾病进展。已有一些应激因素与动物生产和处理有关。作为应激的天然介质,糖皮质激素是一种强大的免疫抑制剂;此外,它们可以与逆转录病毒的长末端重复区结合,并诱导病毒表达。在本研究中,我们报告了一例描述 BLV 感染在自然感染牛中自发重新激活的病例报告。
为了研究 BLV 感染过程中是否在体内发生病毒重新激活,我们对一头慢性 BLV 感染的荷斯坦奶牛(> 3 岁)进行了为期 328 天的随访,该牛具有高前病毒载量。该动物既不产奶也不怀孕。此外,我们还研究了一种应激刺激物(在这种情况下是合成糖皮质激素地塞米松)是否会对另外三头牛的 BLV 感染过程产生影响。我们首次观察到四头慢性 BLV 感染牛的 BLV 转录物水平升高。pol 基因对应的病毒转录物的检测强烈提示这些动物中的病毒重新激活。有趣的是,这种同时的病毒重新激活与地塞米松治疗无关。
我们首次报道了慢性 BLV 感染牛中 BLV 的自发性和高水平转录激活。尽管病毒重新激活与地塞米松治疗无关,但其他应激刺激因素可能对此结果有影响。未来的研究将有必要了解这些观察结果,因为这里报告的自发性病毒重新激活可能对 BLV 发病机制和传播有影响。