Kidd L C, Radke K
Department of Avian Sciences and Biochemistry and Molecular Biology Graduate Group, University of California, Davis 95616-8532, USA.
Virology. 1996 Mar 1;217(1):167-77. doi: 10.1006/viro.1996.0104.
Since bovine leukemia virus (BLV) replicates in B-lymphocytes, viral expression and production should respond to agents activating these cells. We asked whether synthesis of BLV capsid (CA) protein and production of infectious virus would increase when peripheral blood mononuclear cells (PBMCs) from infected sheep were stimulated in short-term culture with lipopolysaccharide (LPS), a polyclonal activator of B-cells, and compared its effects with those of phytohemagglutinin (PHA), a lymphocyte activator known to increase BLV expression. LPS treatment of PBMCs from asymptomatic sheep that had been infected for 1-4 years increased the number of cells synthesizing CA protein, the amount of CA protein per cell, and the number of PBMCs acting as infectious centers. LPS derived from several different microbes was effective. During the ensuing 4 years of asymptomatic infection, the number of PBMCs expressing virus under minimal stimulation increased for each animal. The ability of LPS to recruit additional cells to express CA protein remained constant or decreased in magnitude, yet at the same time, lower concentrations of LPS were required to elicit a maximal effect. This suggests that the cellular pathways affected by LPS are endogenously more activated as infection progresses. PHA initially stimulated fewer cells to synthesize BLV CA protein than LPS did although the amount of CA protein synthesized per cell was greater with PHA. As infection progressed, PHA surpassed LPS in the numbers of PBMCs induced to express CA protein. This suggests that the cellular pathways affected by PHA become more responsive to its effects as infection progresses. LPS increased CA expression early and transiently during culture whereas the PHA-mediated increase continued to develop for several days. Thus, LPS increases BLV expression but does so differently than PHA. Moreover, these longitudinal results show that the activation state of BLV-infected cells changes as asymptomatic infection progresses.
由于牛白血病病毒（BLV）在B淋巴细胞中复制，病毒的表达和产生应该会对激活这些细胞的因子作出反应。我们研究了用脂多糖（LPS）（一种B细胞多克隆激活剂）对感染绵羊的外周血单个核细胞（PBMC）进行短期培养刺激时，BLV衣壳（CA）蛋白的合成和传染性病毒的产生是否会增加，并将其效果与植物血凝素（PHA）（一种已知可增加BLV表达的淋巴细胞激活剂）的效果进行比较。用LPS处理感染1 - 4年的无症状绵羊的PBMC，可增加合成CA蛋白的细胞数量、每个细胞中CA蛋白的量以及作为感染中心的PBMC数量。来自几种不同微生物的LPS均有效。在随后4年的无症状感染期间，每只动物在最小刺激下表达病毒的PBMC数量增加。LPS招募额外细胞表达CA蛋白的能力保持不变或在幅度上有所下降，但与此同时，引发最大效应所需的LPS浓度降低。这表明随着感染进展，受LPS影响的细胞途径在内在水平上被激活得更多。PHA最初刺激合成BLV CA蛋白的细胞比LPS少，尽管PHA处理时每个细胞合成的CA蛋白量更多。随着感染进展，PHA在诱导表达CA蛋白的PBMC数量上超过了LPS。这表明随着感染进展，受PHA影响的细胞途径对其作用变得更敏感。在培养过程中，LPS早期短暂增加CA表达，而PHA介导的增加持续数天。因此，LPS增加BLV表达，但方式与PHA不同。此外，这些纵向结果表明，随着无症状感染的进展，BLV感染细胞的激活状态会发生变化。
