PrPSc binding antibodies are potent inhibitors of prion replication in cell lines
PrPSc binding antibodies are potent inhibitors of prion replication in cell lines
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DOI：
10.1074/jbc.m402270200
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发表时间：
2004-09-17
影响因子：
4.8
通讯作者：
Hawke, S
中科院分区：
文献类型：
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作者：
Beringue, V;Vilette, D;Hawke, S
细胞α-螺旋朊病毒蛋白（PrPC）转化为疾病相关亚型（PrPSc）是朊病毒疾病发病机制的核心。靶向正常或疾病相关亚型的分子可能具有治疗意义，并且已显示结合PrPC的抗体在体外抑制朊病毒积累。在这里，我们调查是否抗体，另外针对疾病相关的亚型，如PrPSc抑制朊病毒复制在绵羊朊蛋白诱导羊瘙痒症感染的Rov细胞。我们从这些实验中得出结论，与另外靶向疾病相关PrP同种型的抗体相比，专门结合PrPC的抗体是ScRov细胞PrPSc积累的相对低效的抑制剂。虽然这些单克隆抗体抑制朊病毒复制的机制尚不清楚，但一些数据表明抗体可能会主动增加PrPSc turnmover。因此，结合正常和疾病相关亚型的抗体代表非常有前途的抗朊病毒剂。
Conversion of the cellular alpha-helical prion protein (PrPC) into a disease-associated isoform (PrPSc) is central to the pathogenesis of prion diseases. Molecules targeting either normal or disease-associated isoforms may be of therapeutic interest, and the antibodies binding PrPC have been shown to inhibit prion accumulation in vitro. Here we investigate whether antibodies that additionally target disease-associated isoforms such as PrPSc inhibit prion replication in ovine PrP-inducible scrapie-infected Rov cells. We conclude from these experiments that antibodies exclusively binding PrPC were relatively inefficient inhibitors of ScRov cell PrPSc accumulation compared with antibodies that additionally targeted disease-associated PrP isoforms. Although the mechanism by which these monoclonal antibodies inhibit prion replication is unclear, some of the data suggest that antibodies might actively increase PrPSc turnmover. Thus antibodies that bind to both normal and disease-associated isoforms represent very promising anti-prion agents.