Spontaneous virus reactivation in cattle chronically infected with bovine leukemia virus

Abstract

Background: 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.

Case presentation: 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.

Conclusions: 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.

Keywords: BLV; Retrovirus; Stress; Transcriptional activation.

Fig. 1

Spontaneous virus reactivation during chronic BLV infection in cattle. The BLV proviral load (black), BLV pol RNA expression (red), level of BLV-sp antibodies (blue dotted line) and the absolute counts of lymphocytes (blue solid line) were followed-up in a single Holstein cow chronically infected with BLV. BLV DNA and RNA levels are expressed as Log₁₀ of copies per μg of total DNA and per ml of plasma, respectively (left axis). BLV-sp Abs were measured by ELISA and are expressed as percent of reactivity (right axis). The dotted horizontal black line represent the limit of detection of BLV qPCR (100 copies per μg). The Figure Insets correspond to a pilot study to assess the effect of a stressor stimuli on BLV infection in cattle. The BLV proviral load (Upper inset) and BLV pol RNA expression (Lower inset) were followed-up in four cattle infected with BLV; three of these cattle received DEX treatment (IDs# 177, 190 and 230) and one was used as an untreated control (Animal 184). All these parameters were measured in peripheral blood. BLV DNA and RNA levels are expressed as Log₁₀ of copies per μg of total DNA and per ml of plasma. The dotted horizontal black line represent the limit of detection of BLV qPCR (100 copies per μg). Black arrows represent DEX administrations