Bovine viral diarrhea virus (BVDV) infects different cell types including antigen-presenting cells such as macrophages. The infection induces pro-inflammatory cytokines like interleukin 1 beta (IL-1β), which is necessary to trigger a successful inflammatory response against infections. Several authors have reported differences between IL-1β gene expression and protein detection in BVDV-infected macrophages. These patterns may be related to inflammasome assembly, which promote the formation of active caspase 1 in order to produce mature IL-1β molecules. Our goal was to assess BVDV ability to induce the release of IL-β through a caspase 1 dependent pathway in bovine macrophages. We infected peripheral blood monocyte-derived macrophages using BVDV NADL strain at 0.001, 0.1, 2 and 10 multiplicities of infection (MOI) and we measured IL-1β at different times 2, 6, 12, 24, 48, 72 h. We found an increase of 1140-2154 pg for a MOI of 10:1 and 2:1 respectively. To inhibit caspase 1, we used either carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD) or carbobenzoxy-tyr-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Y-VAD). We found decreased IL-1β secretion 2154 pg/ml to 854 pg/ml IL-1β secretion using Y-VAD and we observed decrease from 2154 pg/ml to 22.33 pg/ml with Z-VAD, and this inhibition was followed by diminished viral replication from 2.25 × 107 to 2.1 × 105 CCID50, which suggests that caspase 1-dependent secretion of the IL-1β active molecule is important for viral replication. This is the first report showing that BVDV infected-bovine macrophages trigger the caspase 1 dependent pathway for IL-1β activation and that activation increases viral replication.

中文翻译：

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牛病毒性腹泻病毒的NADL株通过胱天蛋白酶1诱导牛巨噬细胞分泌IL-1β。

牛病毒性腹泻病毒（BVDV）感染不同类型的细胞，包括抗原呈递细胞，例如巨噬细胞。感染会诱发促炎性细胞因子，例如白介素1β（IL-1β），这对于触发针对感染的成功炎症反应是必要的。几位作者报道了BVDV感染的巨噬细胞中IL-1β基因表达与蛋白质检测之间的差异。这些模式可能与炎症小体组装有关，后者促进活性胱天蛋白酶1的形成，以产生成熟的IL-1β分子。我们的目标是评估BVDV通过caspase 1依赖性途径在牛巨噬细胞中诱导IL-β释放的能力。我们使用BVDV NADL株以0.001、0.1，2和10多重感染（MOI），我们在2、6、12、24、48、72小时的不同时间测量了IL-1β。我们发现MOI分别为10：1和2：1时增加了1140-2154 pg。为了抑制半胱天冬酶1，我们使用了碳氧苯甲酰-戊基-丙氨酰基-天冬氨酰-[O-甲基]-氟甲基酮（Z-VAD）或碳氧苯甲酰-酪氨酸-戊基-丙氨酰基-天冬氨酰-[O-甲基]-氟甲基酮）。我们发现使用Y-VAD可以将IL-1β分泌从2154 pg / ml降低到854 pg / ml，并且通过Z-VAD可以将IL-1β分泌从2154 pg / ml降低到22.33 pg / ml，并且这种抑制作用随后被减弱了病毒复制从2.25×107到2.1×105 CCID50，这表明IL-1β活性分子的caspase 1依赖性分泌对于病毒复制很重要。