Institute of Virology, Department of Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria.
Institute for Molecular Pharmacology, RWTH Aachen University, 52062 Aachen, Germany.
Viruses. 2022 Feb 13;14(2):381. doi: 10.3390/v14020381.
The entry of BVDV into bovine cells was studied using CRIB cells (cells resistant to infection with bovine viral diarrhea virus [BVDV]) that have evolved from MDBK cells by a spontaneous loss of susceptibility to BVDV. Recently, larger genetic deletions were reported but no correlation of the affected genes and the resistance to BVDV infection could be established. The metalloprotease ADAM17 was reported as an essential attachment factor for the related classical swine fever virus (CSFV). To assess whether ADAM17 might be involved in the resistance of CRIB-1 cells to pestiviruses, we analyzed its expression in CRIB-1 and MDBK cells. While ADAM17 protein was detectable in MBDK cells, it was absent from CRIB-1 cells. No functional full-length ADAM17 mRNA could be detected in CRIB cells and genetic analysis revealed the presence of two defective alleles. Transcomplementation of functional ADAM17 derived from MDBK cells in CRIB-1 cells resulted in a nearly complete reversion of their resistance to pestiviral infection. Our results demonstrate that ADAM17 is a key cellular factor for the pestivirus resistance of CRIB-1 cells and establishes its essential role for a broader range of pestiviruses.
我们使用 CRIB 细胞（对牛病毒性腹泻病毒 [BVDV] 感染具有天然抗性的细胞）研究了 BVDV 进入牛细胞的过程，CRIB 细胞是由 MDBK 细胞自发丧失对 BVDV 的敏感性而进化而来的。最近，报道了更大的基因缺失，但未能确定受影响的基因与对 BVDV 感染的抗性之间的相关性。金属蛋白酶 ADAM17 被报道为相关的经典猪瘟病毒（CSFV）的必需附着因子。为了评估 ADAM17 是否可能参与 CRIB-1 细胞对瘟病毒的抗性，我们分析了其在 CRIB-1 和 MDBK 细胞中的表达。虽然 ADAM17 蛋白可在 MDBK 细胞中检测到，但在 CRIB-1 细胞中不存在。在 CRIB 细胞中未检测到功能性全长 ADAM17 mRNA，遗传分析显示存在两个缺陷等位基因。功能性 ADAM17 来源于 MDBK 细胞在 CRIB-1 细胞中的转染导致其对瘟病毒感染的抗性几乎完全逆转。我们的结果表明，ADAM17 是 CRIB-1 细胞对瘟病毒抗性的关键细胞因子，并确立了其在更广泛的瘟病毒中的重要作用。
