Bovines infected by bovine leukemia virus (BLV) are characterized by presenting low proviral load (LPL) or high proviral load (HPL). It is reported that animals with HPL in peripheral blood mononuclear cells (PBMCs) present a decrease in apoptosis, an increase in viability and the proliferation rate, while animals that maintain an LPL have an intrinsic ability to control the infection, presenting an increased apoptosis rate of their PBMCs. However, there is little information on the effect of BLV on these mechanisms when the virus infects somatic milk cells (SC). This study investigates the mechanisms underlying apoptosis in milk and blood from BLV-infected animals with HPL and LPL. Relative levels of mRNA of tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNF-RI), TNF receptor 2 (TNF-RII), anti-apoptotic B-cell lymphoma 2 protein (Bcl-2), and pro-apoptotic Bcl-2-like protein 4 (Bax) were measured in SC and PBMCs using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. A significant decrease in the expression of TNF-α in SC from HPL animals vs non-infected bovines was observed, but the infection in SC with BLV did not show a modulation on the expression of TNF receptors. A significant increase in TNF-RI expression in PBMCs from HPL bovines compared to LPL bovines was observed. No significant differences in PBMCs between HPL and LPL compared to non-infected animals concerning TNF-α, TNF-RI, and TNF-RII expression were found. There was a significant increase of both Bcl-2 and Bax in SC from LPL compared to non-infected bovines, but the Bcl-2/Bax ratio showed an anti-apoptotic profile in LPL and HPL bovines compared to non-infected ones. Reduced mRNA expression levels of Bax were determined in the PBMCs from HPL compared to LPL subjects. In contrast, BLV-infected bovines did not differ significantly in the mRNA expression of Bax compared to non-infected bovines. Our data suggest that the increased mRNA expression of Bax corresponds to the late lactation state of bovine evaluated and the exacerbated increase of mRNA expression of Bcl-2 may be one of the mechanisms for the negative apoptosis regulation in the mammary gland induced by BLV infection. These results provide new insights into the mechanism of mammary cell death in HPL and LPL BLV-infected bovine mammary gland cells during lactation.

感染牛白血病病毒（BLV）的牛的特征是呈现低原病毒载量（LPL）或高原病毒载量（HPL）。据报道，外周血单核细胞（PBMC）中具有HPL的动物表现出细胞凋亡减少、活力和增殖率增加，而维持LPL的动物具有控制感染的内在能力，表现出细胞凋亡率增加他们的 PBMC。然而，当病毒感染体乳细胞（SC）时，关于 BLV 对这些机制的影响的信息很少。本研究调查了 BLV 感染动物的乳汁和血液中 HPL 和 LPL 细胞凋亡的机制。肿瘤坏死因子-α (TNF-α)、TNF 受体 1 (TNF-RI)、TNF 受体 2 (TNF-RII)、抗凋亡 B 细胞淋巴瘤 2 蛋白 (Bcl-2) 和 mRNA 的相对水平使用定量逆转录聚合酶链反应 (RT-qPCR) 测定 SC 和 PBMC 中的促凋亡 Bcl-2 样蛋白 4 (Bax)。与未感染的牛相比，观察到 HPL 动物 SC 中 TNF-α 表达显着降低，但用 BLV 感染 SC 并没有显示出对 TNF 受体表达的调节。与 LPL 牛相比，HPL 牛的 PBMC 中 TNF-RI 表达显着增加。与未感染动物相比，HPL 和 LPL 之间的 PBMC 在 TNF-α、TNF-RI 和 TNF-RII 表达方面没有发现显着差异。与未感染的牛相比，LPL 牛的 SC 中的 Bcl-2 和 Bax 显着增加，但与未感染的牛相比，LPL 和 HPL 牛中的 Bcl-2/Bax 比率显示出抗凋亡特征。与 LPL 受试者相比，HPL 受试者的 PBMC 中 Bax mRNA 表达水平降低。相比之下，BLV感染的牛与未感染的牛相比，Bax mRNA表达没有显着差异。我们的数据表明，Bax mRNA表达的增加对应于所评估的牛的泌乳后期状态，并且Bcl-2 mRNA表达的加剧增加可能是BLV感染诱导的乳腺负性凋亡调节的机制之一。这些结果为HPL和LPL BLV感染的牛乳腺细胞在哺乳期间乳腺细胞死亡的机制提供了新的见解。