Heeney J L, Valli P J, Jacobs R M, Valli V E
Department of Chronic and Infectious Diseases, Institute of Applied Radiobiology and Immunology TNO, Rijswijk, The Netherlands.
Lab Invest. 1992 May;66(5):608-17.
Bovine leukemia virus (BLV) infection of cattle is a common but inapparent retrovirus infection from which less than 5% of infected cattle manifest clinically with lymphoma. During the course of life-long infection, cattle maintain a high anti-BLV titer during an apparent latent infection of B cells from which proviral DNA but not transcripts can be detected. To investigate if BLV infection is truly latent and restricted only to B lymphocytes, peripheral blood leukocytes were purified from cattle with naturally acquired BLV infection with various stages of subclinical and clinical disease. These cells were purified into populations of polymorphonuclear cells, monocytes and subsequently B cells and T cells by fluorescent-activated cell sorting. Southern blot analysis revealed the presence of provirus in monocytes and B cells but not T cells. Secondly, the ability of provirus containing cell types to express BLV antigens was then confirmed by mitogen stimulation in vitro. Subsequently, the pattern of expression of BLV antigens was studied in situ in tissue sections to determine the location of BLV antigen expressing cells in vivo. Antigen expressing cells were infrequent and solitary in intrafollicular and marginal zone cells of architecturally normal lymph nodes of chronic, BLV-infected cattle. These results demonstrate that BLV persists in cells of the monocyte/macrophage lineage in addition to B lymphocytes and that expression of BLV antigens in cattle doses occur but rarely in lymph nodes of BLV infected cattle. The high frequency of provirus containing cells and infrequent expression of BLV antigen in vivo suggests that BLV expression is not truly latent but highly regulated, possibly triggered by rare events in host lymphoid tissue.
牛白血病病毒（BLV）感染牛群很常见，但属于隐性逆转录病毒感染，不到5%的感染牛会出现淋巴瘤临床症状。在终生感染过程中，牛在B细胞明显潜伏感染期间维持高抗BLV滴度，在此期间可检测到前病毒DNA，但检测不到转录本。为了研究BLV感染是否真的潜伏且仅局限于B淋巴细胞，从患有不同亚临床和临床疾病阶段的自然感染BLV的牛中纯化外周血白细胞。通过荧光激活细胞分选将这些细胞纯化分为多形核细胞、单核细胞群体，随后分为B细胞和T细胞群体。Southern印迹分析显示单核细胞和B细胞中存在前病毒，而T细胞中不存在。其次，通过体外有丝分裂原刺激证实了含前病毒细胞类型表达BLV抗原的能力。随后，在组织切片中原位研究BLV抗原的表达模式，以确定体内表达BLV抗原细胞的位置。在慢性BLV感染牛结构正常淋巴结的滤泡内和边缘区细胞中，抗原表达细胞很少且呈孤立状态。这些结果表明，除了B淋巴细胞外，BLV还存在于单核细胞/巨噬细胞谱系的细胞中，并且在感染BLV的牛的淋巴结中确实会出现BLV抗原的表达，但很少见。体内含前病毒细胞的高频率和BLV抗原的罕见表达表明，BLV的表达并非真的潜伏，而是受到高度调控，可能由宿主淋巴组织中的罕见事件触发。
